US20230322925A1 - Phospholipid ether (ple) car t cell tumor targeting (ctct) agents - Google Patents
Phospholipid ether (ple) car t cell tumor targeting (ctct) agents Download PDFInfo
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- US20230322925A1 US20230322925A1 US18/189,433 US202318189433A US2023322925A1 US 20230322925 A1 US20230322925 A1 US 20230322925A1 US 202318189433 A US202318189433 A US 202318189433A US 2023322925 A1 US2023322925 A1 US 2023322925A1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title claims description 29
- 206010028980 Neoplasm Diseases 0.000 title claims description 15
- 150000003904 phospholipids Chemical class 0.000 title claims description 5
- 230000008685 targeting Effects 0.000 title abstract 2
- 239000003795 chemical substances by application Substances 0.000 title 1
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- 210000004881 tumor cell Anatomy 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 6
- -1 terpenoid lipid Chemical class 0.000 claims description 180
- 210000004027 cell Anatomy 0.000 claims description 49
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 39
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 34
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 25
- 150000002632 lipids Chemical class 0.000 claims description 25
- 125000006850 spacer group Chemical group 0.000 claims description 25
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- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 4
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- 150000003905 phosphatidylinositols Chemical class 0.000 claims description 4
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 229920002732 Polyanhydride Polymers 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 57
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- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 40
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Definitions
- the alternatives described herein pertain to synthetic compounds that are designed to target and selectively decorate tumor cell membranes so as to facilitate recognition by binding agents.
- the synthetic compounds have recognition moieties that interact with specific Chimeric Antigen Receptor T cells (CAR T cells), in which both the synthetic compounds and the CAR T cells are administered to a subject by intravenous or locoregional administration.
- CAR T cells Chimeric Antigen Receptor T cells
- Chimeric receptors are synthetic receptors that include an extracellular ligand binding domain, most commonly a single chain variable fragment of a monoclonal antibody (scFv) linked to intracellular signaling components, most commonly CD3 ⁇ alone or combined with one or more costimulatory domains.
- scFv monoclonal antibody
- Much of the research in the design of chimeric receptors has focused on defining scFvs and other ligand binding elements that target malignant cells without causing serious toxicity to essential normal tissues, and on defining the optimal composition of intracellular signaling modules to activate T cell effector functions.
- CAR T cell-mediated therapy that is selective for specific targets and which minimizes adverse side effects.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is a carbon chain or a fatty acid such as an aliphatic chain.
- the carbon chain or fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or it comprises an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the hapten which is a target moiety, comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene),, 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), St
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid further comprises a spacer that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a Hapten (2x) spacer, a Hapten (3x) spacer, a Hapten (4x) spacer, a Hapten (5x) spacer, or an alkane chain.
- the spacer comprises poly(carboxybetaine), peptides, polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone or Poly(ethylene oxide).
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell.
- the target cell exists in a tumor microenvironment.
- a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) is provided, wherein the CAR or TCR is bound to a lipid, wherein the lipid comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is a carbon chain or a fatty acid such as an aliphatic chain.
- the carbon chain or fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or it comprises an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid further comprises a spacer group that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a Hapten (2x) spacer, a Hapten (3x) spacer, a Hapten (4x) spacer, a Hapten (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell.
- the target cell exists in a tumor microenvironment.
- the hapten which is a target moiety, comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Struc
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprising: a) introducing, providing, or administering to a subject a composition that comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optional
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as a carbon chain or an aliphatic chain. In some alternatives, the carbon chain or fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the spacer comprises a PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the masking moiety comprises a phenolic hydroxyl group or PEG.
- the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein.
- the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment.
- the cleavable moiety which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36, 48, 60 or 72 hours after administration of the composition, or any time within a range defined by any two aforementioned values.
- the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36 or 48 hours before administration of the composition, or any time within a range defined by any two aforementioned values.
- the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject.
- a boost of the cell and/or the composition is provided to the subject.
- an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cell comprising the CAR or TCR is a T cell.
- the CAR or TCR is on the surface of the cell or the T cell.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid intercalates in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- the hapten which is a target moiety, comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene),, 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), St
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- a composition comprising a lipid, and wherein the lipid comprises a target moiety that is bound to a masking moiety.
- the target is bound to the masking moiety through a spacer.
- the masking moiety is removed when the composition is in a tumor microenvironment.
- the masking moiety is removed when the composition is in a ROS rich tumor environment.
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprises: a) introducing, providing, or administering to a subject the composition of any one of the alternatives herein, wherein the composition comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps
- the composition comprises a lipid, wherein the lipid comprises a target moiety that is bound to a masking moiety. In some alternatives, the target is bound to the masking moiety through a spacer. In some alternatives, the masking moiety is removed when the composition is in a tumor microenvironment. In some alternatives, the masking moiety is removed when the composition is in a ROS rich tumor environment. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether (PLE).
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain.
- the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 18 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the spacer comprises a PEG spacer, a Hapten (2x) spacer, a Hapten (3x) spacer, a Hapten (4x) spacer, a Hapten (5x) spacer,or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the masking moiety comprises a phenolic hydroxyl group or PEG.
- the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein.
- the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment.
- the cleavable moiety, which is configured to be cleavable in a tumor microenvironment is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36, 48, 60 or 72 hours after administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36 or 48 hours before administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject. In some alternatives, a boost of the cell and/or the composition is provided to the subject.
- an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cell comprising the CAR or TCR is a T cell. In some alternatives, the CAR or TCR is on the surface of the cell or the T cell.
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid intercalates in a lipid bilayer of a target cell.
- the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the masking moiety is removed when the composition is within an acidic environment. In some alternatives, the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values. In some alternatives, the masking moiety is removed by nitrosylation.
- the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-tria
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR), wherein the CAR or TCR is joined to a peptide (which, optionally, may comprise one or more haptens joined thereto, e.g., by way of covalent or disulfide bonds), an antibody or binding fragment thereof through a CAR or TCR-mediated interaction with said target moiety and, wherein said antibody or binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell.
- CAR chimeric antigen receptor
- TCR T cell receptor
- said target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)).
- the CAR or TCR is expressed by a cell or a T cell.
- the CAR or TCR is on the surface of a cell or a T cell.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the peptide, which comprises a target moiety, such as fluorescin is an albumin, a mutant albumin, or a fragment thereof, a cyclic peptide PEGA, or CREKA.
- the antibody or binding fragment thereof, which comprises a target moiety, such as fluorescin is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimum
- the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-tria
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) is provided, wherein the CAR or TCR is configured to bind with an antibody or binding fragment thereof comprising a target moiety through a CAR or TCR-mediated interaction with said target moiety and, wherein said antibody or binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell.
- CAR chimeric antigen receptor
- TCR T cell receptor
- said target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein (e.g., Fluorescein isothiocyanate (FITC)).
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNC
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprises a) introducing, providing, or administering to a subject a composition that comprises an antibody or binding fragment thereof, which comprises a target moiety such as, a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein (e.g., Fluorescein isothiocyanate (FITC)); and b) introducing, providing, or administering to said subject a cell that comprises a chimeric antigen receptor (CAR) or T cell receptor (TCR), wherein the CAR or TCR is specific for the target moiety.
- a target moiety such as, a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigen
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the antibody or binding fragment thereof, which comprises the target moiety is specific for a target or selected cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the target immune cell is a T cell or a B cell.
- the target cell exists in a tumor microenvironment.
- the antibody or binding fragment thereof, which comprises the target moiety is specific for a viral or bacterial antigen.
- the cell comprises a chimeric antigen receptor (CAR) or T cell receptor (TCR), wherein the CAR or TCR is configured to bind with an antibody or binding fragment thereof comprising a target moiety through a CAR or TCR-mediated interaction with said target moiety and, wherein said antibody or binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell.
- said target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein (e.g., Fluorescein isothiocyanate (FITC)).
- FITC Fluorescein isothiocyanate
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives of the method, the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject.
- a boost of the cell and/or the composition is provided to the subject.
- an additional therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the antibody or binding fragment thereof, which is conjugated to the target moiety is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontict
- the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-tria
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- a method of screening cells that comprise a CAR or TCR whereby cells, such as T cells, which comprise a CAR or TCR are evaluated for the ability to bind or interact with a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), which is present on a substrate, such as a membrane, bead, or support (e.g., a well) or a binding agent, such as a lipid (e.g., PLE), hapten, ligand, or antibody, or binding fragment thereof, preferably a binding agent that has specificity for an hapten, poly(his)
- the substrate or binding agent comprising the desired target moiety is contacted with a plurality of cells comprising a CAR or TCR specific for said target moiety and the level or amount of binding of the cells comprising the CAR or TCR to the target moiety present on the substrate or binding agent is determined.
- Such an evaluation of binding may include staining for cells bound to target moieties or evaluation of fluorescence or loss of fluorescence.
- a target cell is also provided such that the method comprises contacting a cell, such as a T cell, which comprises a CAR or TCR that is specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), with a binding agent such as a hapten, ligand, or antibody or antibody fragment thereof joined to said target moiety in the presence of a target cell, such as a cancer cell or bacterial cell, or a target virus and evaluating the binding of the cell comprising the CAR or TCR to the binding agent and/or evaluating the binding of the cell comprising the CAR or TCR to the target cell or target virus
- a complex and the complex itself comprising a cell, such as a T cell, which comprises a CAR or TCR specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), joined to a binding agent, such as a hapten, ligand, or antibody or antibody fragment thereof comprising said target moiety, through a CAR or TCR mediated binding to said target moiety, wherein said binding agent is further bound to or interacts with a target cell, such as a cancer cell or bacterial cell, or a target virus are contemplated.
- a target moiety such as a hapten, poly(his) tag
- the antibody or binding fragment thereof, which is conjugated to the target moiety is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontict
- the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-tria
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- FIGS. 1 A and 1 B shows the initial phospholipid ether (PLE) CAR T cell tumor targeting or cancer cell targeting (CTCT) agents.
- CTCT cancer cell targeting
- FL-PLE 1A
- ProFL-PLE ProFL-PLE
- FL fluorescein
- PEG Polyetheneglycol
- PLE iii is the polar head group
- iv is the hydrophobic tail for incorporation or tethering into the cell plasma membrane.
- Masking moiety to prevent anti-FLCAR T cell recognition.
- FIG. 2 shows the schematic of FL-PLE and ProFL-PLE.
- (a) shows that a PLE is embedded into a lipid raft on the cell membrane of a tumor cell.
- (b) is a FL-PLE with a single PEG spacer compared to a four PEG spacer that is shown in (c). The PEG spacer will be varied until the optimal spacer length to antiFL CAR T-cell pair is identified.
- (d) is a ProFL-PLE containing a steric hindrance “masking” moiety and an “optimal” PEG spacer.
- (e) is the conversion of ProFL-PLE to FL-PLE due to masking moiety cleavage once inside the ROS rich tumor microenvironment. The FL-PLE is now bioavailable to antiFL CAR T-cells.
- FIG. 3 shows the synthesis routes for FL-PLE.
- FIG. 4 shows the resulting NMR data in a 1D NMR spectra of the synthesized FL-PLE, which was subjected to NMR analysis.
- the 1D-spectra from the NMR identified the synthesized product as FL-PLE that was shown in the synthesis of FIG. 3 .
- FIG. 5 shows Synthesis Routes for ProFL-PLE.
- FIG. 6 shows the NMR of ProFL-PLE.
- the Synthesized ProFL-PLE was subjected to NMR analysis. Spectra from the NMR identify the synthesized product as ProFL-PLE that was shown in the synthesis of FIG. 5 .
- FIGS. 7 A- 7 E shows tumor targeting & integration of FL-PLE.
- (7A-7D) Cells were incubated with 5 ⁇ M FL-PLE overnight then cells were analyzed by flow or confocal microscope. The cells may also be incubated with 1 nM, 5 nM, 10 nM, 100 nM, 200 nM, 300 nM 400 nM, 500 nM, 600 nM, 700 nM, 800 nM, 1 ⁇ M, 5 ⁇ M, 10 ⁇ M, 15 ⁇ M, 20 ⁇ M or 25 ⁇ M FL-PLE overnight. The level of FL-PLE integration into the cell membrane was identified by the signal intensity emitted from the fluorescein moiety of the FL-PLE.
- the cells may be incubated with 1 nM, 5 nM, 10 nM, 100 nM, 200 nM, 300 nM 400 nM, 500 nM, 600 nM, 700 nM, 800 nM, 1 ⁇ M, 5 ⁇ M, 10 ⁇ M, 15 ⁇ M, 20 ⁇ M or 25 ⁇ M FL-PLE
- 7D Confocal images show that FL-PLE integrates over the whole cell surface (U87 cells). The FL-PLE is shown in green and the nucleus is stained with DAPI which is shown in blue.
- 7E After a glioblastoma (U87 cells) tumor was established in a group of mice by intracranial injection, the mice received an intravenous injection of FL-PLE.
- mice were sacrificed and brains were harvested at various time points post FL-PLE injection.
- the fluorescent image of a brain harvested 2 days post FL-PLE injection demonstrates that FL-PLE preferentially targets and integrates into the tumor in an in vivo environment.
- the FL-PLE is in a targeted area as demonstrated by the circular area within the right quadrant of the brain shown in FIG. 7 E .
- FIG. 8 shows that the FL moiety is accessible for binding.
- U87 cells were incubated with 5 ⁇ M FL-PLE overnight then imaged by confocal microscopy. Same as FIG. 7 D except this time U87 cells (nucleus shown in blue, DAPI) with FL-PLE (green) integrated into the membrane were stained with an antifluorescein antibody conjugated with an Alex 647 fluorophore (grey). These images demonstrate that the FL moiety is accessible for binding. As shown in FIG. 8 , the anti-FL antibody is bound to the FL-PLE.
- FIGS. 9 A- 9 C shows the results of CAR T cell recognition and activation through FL-PLE (in vitro).
- K562 leukemia
- FL-PLE in vitro
- the specific lysis was the same for the CD8+ mock cells and the CD8+ AntiFL CAR bearing cells.
- the CD8+ AntiFL CAR cells showed a higher percentage of specific lysis.
- the CD8+ antiFL CAR cells exhibited better Il-2, TNF ⁇ and IFN ⁇ release than the CD8+ mock cells.
- FIG. 10 shows the results of CAR T cell recognition and activation through FL-PLE (in vivo).
- Winn Assay U87 cells harboring a green fluorescent protein and firefly luciferase fusion protein (GFP-ffLuc) were incubated with FL-PLE overnight. Note, the GFP-ffLuc allows for real-time monitoring of tumor progression via luminescent imaging. These cells were then mixed with CD8+ antiFL CAR T cells or CD8+ mock T cells at a 1:1 or 10:1 effector to target (E:T) ratio. Cell mixtures were injected into the brain of a mouse and tumor engraftment was monitored by luminescent flux over time. Here the antiFL CAR T cell is able to activate and slow down the engraftment of the tumor at a 10:1 (E:T). This demonstrates that the FL-PLE works as a target for CAR T-cell recognition in a living model.
- E:T effector to target
- FIG. 11 shows ProFL-PLE integration into cells and unmasking.
- U87 cells were incubated with 5 ⁇ M ProFL-PLE overnight then imaged by confocal microscopy. The nucleus of the cells were stained with DAPI (blue). Same procedure as FIG. 5 D .
- ProFL-PLE is not fluorescent due to the presence of the masking agent, a phenolic hydroxy group.
- the masking agent a phenolic hydroxy group.
- the unmasked ProFL-PLE has the capability to emit green fluorescence (green).
- FIG. 12 shows an example of a construction scheme for the synthesis of fluorescein-PEG-phosphatidylcholine.
- FIG. 13 shows an example of a construction scheme for the synthesis of fluorescein-PEG.
- FIG. 14 shows the construction scheme for ProFL-NHS.
- FIG. 15 shows a commercially available ROS detection system. As shown, a development of novel fluorescence probes can reliably detect reactive oxygen species and distinguish specific species. (Journal of Biological Chemistry 2003 278(5) 3170-3175, incorporated by reference in its entirety herein).
- the term “about” indicates that a value includes the inherent variation of error for the method being employed to determine a value, or the variation that exists among experiments.
- Chimeric antigen receptor or “CAR” or “Chimeric T cell receptor have their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a synthetically designed receptor comprising a ligand binding domain of an antibody or other protein sequence that binds to a molecule associated with the disease or disorder and is linked via a spacer domain to one or more intracellular signaling domains of a T cell or other receptors, such as a costimulatory domain.
- Chimeric receptor can also be referred to as artificial T cell receptors, chimeric T cell receptors, chimeric immunoreceptors, and chimeric antigen receptors (CARs).
- CARs are engineered receptors that can graft an arbitrary specificity onto an immune receptor cell.
- the term chimeric antigen receptors or “CARs” are also considered by some investigators to include the antibody or antibody fragment, the spacer, signaling domain, and transmembrane region.
- the epitope binding region for example, antibody fragment, scFv, or portion thereof
- spacer, transmembrane domain, and/ or signaling domain the components of the CAR are frequently distinguished throughout this disclosure in terms of independent elements.
- the spacer for the chimeric antigen receptor is selected (e.g., for a particular length of amino acids in the spacer) to achieve desired binding characteristics for the CAR.
- CARs having varying lengths of spacers, e.g., presented on cells are then screened for the ability to bind or interact with a target moiety to which the CAR is directed.
- target moieties include a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)).
- GFP green fluorescent protein
- FITC Fluorescein isothiocyanate
- the target moieties to which the CARs bind or interact can be presented on a substrate, such as a membrane, bead, or support (e.g., a well) or a binding agent, such as a lipid (e.g., PLE), hapten, ligand, or antibody, or binding fragment thereof, preferably a binding agent that has specificity for an antigen present on a cancer cell or pathogen such as, a virus or bacteria.
- a substrate or binding agent comprising the desired target moiety is contacted with a plurality of cells comprising a CAR or TCR specific for said target moiety and the level or amount of binding of the cells comprising the CAR or TCR to the target moiety present on the substrate or binding agent is determined.
- a target cell is also provided such that the method comprises contacting a cell, such as a T cell, which comprises a CAR or TCR that is specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), with a binding agent such as a hapten, ligand, or antibody or antibody fragment thereof joined to said target moiety in the presence of a target cell, such as a target cell, such as a T cell, which comprises a CAR or TCR that is specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag,
- the antibody or binding fragment thereof, which is conjugated to the target moiety, used in these evaluations comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab
- Co-stimulatory domain has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a signaling moiety that provides to T cells a signal which, in addition to the primary signal provided by for instance the CD3 zeta chain of the TCR/CD3 complex, mediates a T cell response, including, but not limited to, activation, proliferation, differentiation, cytokine secretion, and the like.
- a co-stimulatory domain can include all or a portion of, but is not limited to, CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83.
- the co-stimulatory domain is an intracellular signaling domain that interacts with other intracellular mediators to mediate a cell response including activation, proliferation, differentiation and cytokine secretion, and the like.
- the co-stimulatory domain comprises 41bb and CD3zeta.
- a T cell comprising a CAR specific for the targeting moiety on the composition.
- the T cell further comprise an 806 CAR (anti-EGFR(806)(41BB-CD3zeta CAR).
- the CAR is specific for a lipid or peptide that targets a tumor or cancer cell, wherein the lipid or peptide comprises a target moiety and the CAR can specifically bind to said lipid through an interaction with said target moiety.
- the lipid is a phospholipid ether.
- the CAR is specific for a phospholipid ether, wherein the phospholipid ether comprises a target moiety and the CAR specifically binds to said phospholipid ether through an interaction with said target moiety.
- the CAR comprises a co-stimulatory domain.
- the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof.
- LFA-1 lymphocyte function-associated antigen-1
- the CAR is specific for a target moiety affixed to an antibody or binding fragment thereof, wherein the CAR specifically binds to said antibody or binding fragment thereof through an interaction with said target moiety.
- target moieties which can be conjugated to said antibody or binding fragment thereof include a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)).
- GFP green fluorescent protein
- FITC Fluorescein isothiocyanate
- the antibody or binding fragment thereof is specific for an antigen or ligand present on a cancer cell or a pathogen (e.g., viral or bacterial pathogen). In some alternatives, the antibody or binding fragment thereof is specific for an antigen or ligand present on a tumor cell, a virus, preferably a chronic virus (e.g., a hepatitis virus, such as HBV or HCV, or HIV), or a bacterial cell. In some alternatives herein, the CAR comprises a co-stimulatory domain.
- the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof.
- LFA-1 lymphocyte function-associated antigen-1
- the antibody or binding fragment thereof, which is joined to said target moiety comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictu
- the chimeric receptor nucleic acid comprises a polynucleotide coding for a transmembrane domain.
- the transmembrane domain provides for anchoring of the chimeric receptor in the membrane.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to a lipid wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- CAR chimeric antigen receptor
- TCR T cell receptor
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to an antibody or binding fragment thereof, wherein the antibody or binding fragment thereof comprises a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety.
- a target moiety e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol
- the antibody or binding fragment thereof is further joined to an antigen or ligand present on a cancer cell or a pathogen (e.g., viral or bacterial pathogen).
- the antibody or binding fragment thereof is joined to an antigen or ligand present on a tumor cell, a virus, preferably a chronic virus (e.g., a hepatitis virus, such as HBV or HCV, or HIV), or a bacterial cell.
- the CAR comprises a co-stimulatory domain.
- the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof.
- LFA-1 lymphocyte function-associated antigen-1
- the target moiety is present on an antibody or binding fragment thereof, which are specific for an antigen on a cancer cell or pathogen (e.g., a virus or bacterial cell), and said target moiety is bound by a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- a cancer cell or pathogen e.g., a virus or bacterial cell
- a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- T cell receptor or “TCR” has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a molecule that is found on the surface of T lymphocytes or T cells that is responsible for the recognition of fragments of antigen bound to a major histocompatibility complex molecule.
- Target moiety has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a specific group or site on a molecule or chemical that is a binding target for another chemical or protein of interest.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)).
- GFP green fluorescent protein
- FITC Fluorescein isothiocyanate
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to a lipid wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- CAR chimeric antigen receptor
- TCR T cell receptor
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to an antibody or binding fragment thereof, wherein the antibody or binding fragment thereof comprises a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety.
- a target moiety e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol
- the antibody or binding fragment thereof is further joined to an antigen or ligand present on a cancer cell or a pathogen (e.g., viral or bacterial pathogen).
- the antibody or binding fragment thereof is joined to an antigen or ligand present on a tumor cell, a virus, preferably a chronic virus (e.g., a hepatitis virus, such as HBV or HCV, or HIV), or a bacterial cell.
- the CAR comprises a co-stimulatory domain.
- the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof.
- LFA-1 lymphocyte function-associated antigen-1
- the target moiety is present on an antibody or binding fragment thereof, which are specific for an antigen on a cancer cell or pathogen (e.g., a virus or bacterial cell), and said target moiety is bound by a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- a cancer cell or pathogen e.g., a virus or bacterial cell
- a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- Biotin has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a water-soluble B-vitamin.
- biotin is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor.
- the lipid is a phospholipid ether.
- DNP has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an organic compound with the formula HOC 6 H 3 (NO 2 ) 2 .
- DNP is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor.
- the lipid is a phospholipid ether.
- Fluorescein and fluorescein derivitives has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a synthetic organic compound that is soluble in water and alcohol. It is widely used as a fluorescent tracer for many applications.
- fluorescein is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor.
- the lipid is a phospholipid ether.
- fluorescein is a target moiety on an antibody or binding fragment thereof, which are specific for an antigen on a cancer cell or pathogen (e.g., a virus or bacterial cell), and said target moiety is bound by a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- a cancer cell or pathogen e.g., a virus or bacterial cell
- a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- lipid has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a class of organic compounds that comprise carbon chains, fatty acids or a fatty acid derivative that is typically insoluble in water but can integrate into or mix with hydrophobic or organic solvents.
- lipids can include fats, waxes, fat soluble vitamins, monoglycerides, diglycerides, triglycerides, sphingolipids, cerebrosides, ceramides, and phospholipids.
- amphiphilic lipids that can have a polar head group and a hydrophobic moiety or hydrophobic group.
- Hydrophobic group or hydrophobic moiety has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a molecule or a part of a molecule that is repelled from a mass of water and tends to be non-polar. This can include alkanes, oils and fats.
- lipids can be glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids and polyketides.
- a complex is provided, wherein the complex comprises a lipid.
- the lipid comprises a polar head group and a hydrophobic moiety.
- the hydrophobic moiety is a hydrophobic carbon tail. In some alternatives the hydrophobic carbon tail is saturated or unsaturated. In some alternatives, the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value. In some alternatives, the hydrophobic moiety is a steroid or a cholesterol. In some alternatives, the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid contains branched alkyl tails.
- the lipid can be a sphingolipid.
- the sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine.
- a sphingolipid with an R group consisting of a hydrogen atom only is a ceramide.
- Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
- the lipid is a glycosphingolipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group comprises a fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the lipid is a single chain alkylphospholipid.
- the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine.
- the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine.
- Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- a choline within the polar head group can be substituted with a piperidine moiety.
- the lipid is an anticancer alkylphospholipid.
- Anticancer phospholipids are described by vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- the lipids provided herein are synthetic and structurally related antitumor agents that interact with a cell membrane. These types of synthetic lipids are alkylphospholipids and are described by e.g., van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein). Without being limiting, the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and Erufosine.
- the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine.
- the lipid is a stable analog of lysophosphatidylcholine.
- the lipid is a thio-ether variant of edelfosine, or 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine.
- the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- “Polar-head group” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, the hydrophilic group of a lipid, such as a phospholipid.
- “Phospholipids” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a specific class of lipids that can form lipid bilayers due to their amphiphilic characteristic.
- the phospholipid molecule comprises at least one hydrophobic fatty acid “tail” and a hydrophilic “head” or “polar-head group.”
- the phospholipid or phospholipid ether comprises a polar-head group.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar-head group (e.g., comprising an aromatic ring) and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- a complex is provided, wherein the complex comprises a lipid.
- the lipid comprises a polar head group.
- the lipid is a phospholipid ether.
- the phospholipid ether comprises a target moiety and the CAR is joined to said phospholipid ether through an interaction with said target moiety.
- the phospholipid ether comprises a polar-head group and a carbon alkyl chain.
- the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid is a phospholipid ether.
- the sugar is a glycerol.
- the polar head group comprises a sugar group.
- the lipid comprises a mannose-containing head group.
- the polar head group comprises sphingosine. In some alternatives, the polar head group comprises a glucose. In some alternatives, the polar head group comprises a di-, tri- or tetra-saccharide. In some alternatives, the lipid is a glucosylcerebroside. In some alternatives, the lipid is a lactosylceramide. In some alternatives, the lipid is a glycolipid. In some alternatives, the glycolipid comprises sugar units such as n-glucose, n-galactose or N-actyl-n-galactosamine. In some alternatives, the lipid comprises a hydrocarbon ring such as a sterol.
- the polar head group of the lipid comprises glycerol. In some alternatives, the polar head group of the lipid comprises a phosphate group. In some alternatives, the polar head group of the lipid comprises choline. In some alternatives, the lipid is a phosphatidylethanolomine. In some alternatives, the lipid is a phosphatidylinositol. In some alternatives, the lipid comprises a sphingoid base backbone. In some alternatives, the lipid comprises a sterol lipid, such as cholesterol or its derivatives. In some alternatives, the lipid comprises saccharolipids. In some alternatives, the polar head group comprises choline, phosphate and/or glycerol.
- the lipid is a glycolipid. In some alternatives, the lipid comprises a sugar. In some alternatives, the lipid is derived from sphingosine. In some alternatives, the lipid is a glycerol-glycolipid or a sphingo-glycolipid.
- the lipid is an ether lipid with branched hydrophobic chains.
- “Saturated” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a fatty acid molecule, in which there are no double bonds within the carbon molecules. Unsaturated as described herein indicates that there are one or more double bonds in a fatty acid chain.
- a complex comprising a lipid is provided.
- the lipid comprises a fatty acid chain, in which the fatty acid is saturated or unsaturated.
- Alkyl has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an alkyl substituent that has a missing hydrogen.
- alkenyl has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an unsaturated hydrocarbon that contains at least one carbon-carbon double bond.
- alkynyl has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an unsaturated hydrocarbon containing at least one carbon-carbon triple bond.
- Tepenoid has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a molecule that is derived from five carbon isoprene units. Steroids and sterols can be produced from terpenoid precursors. For example steroids and cholesterol can be biosynthesized by terpenoid precursors.
- Phospholipid ether has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a lipid in which one or more of the carbon atoms on a polar head group are bonded to an alkyl chain via an ether linkage as opposed to the more common ester linkage.
- the polar head group is a glycerol.
- Antibody has its plain and ordinary meaning when read in light of the specification.
- the term antibody refers to an antibody and in some circumstances refers to a binding fragment of an antibody.
- a labeled antibody includes an antibody or binding fragment thereof, in some circumstances, joined to a detectable moiety (for example, a target moiety such as, a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC))).
- GFP green fluorescent protein
- FITC Fluorescein isothiocyanate
- the labeled antibody or binding fragment thereof described herein includes an antibody or binding fragment thereof that specifically binds an antigen of a cancer cell or an antigen of a pathogen.
- Non-limiting examples of an antibody or binding fragment thereof, which can be conjugated with target moieties include monoclonal antibodies, bispecific antibodies, Fab, Fab2, Fab3, scFv, Bis-scFv, minibody, triabody, diabody, tetrabody, VhH domain, V-NAR domain, IgNAR, and camel Ig. Additional examples of an antibody are IgG (e.g., IgG1, IgG2, IgG3, or IgG4), IgM, IgE, IgD, and IgA.
- Non-limiting examples of antibodies include human antibodies, humanized antibodies, or chimeric antibodies.
- Non-limiting examples of recombinant antibodies include antibodies that specifically bind to NGF.
- An antibody or binding fragment thereof that specifically binds an antigen of a cancer cell, which can be conjugated with target moieties may include, for example, abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvet
- Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the cancer cells having the antigen specific for the antibodies or binding fragments thereof.
- a target moiety e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag
- any of the cancer specific antibodies described herein may bind an antigen on a cancer cell, for example on a tumor cell.
- Specific tumor cell antigens to which antibodies can be generated, which can be conjugated with target moieties may include, for example, angiopoietins, transmembrane receptors, cell adhesion molecules, cluster of differentiation molecules, gangliosides, glycoproteins, growth factors, integrins, interleukins, Notch receptors, syn-notch receptors, syn-notch, transmembrane glycoproteins, tumor necrosis factors, or tyrosine kinases.
- a tumor cell antigen may include, for example, 5T4, B7-H3, carbonic anhydrase IX, carcinoembryonic antigen, CA-125, CD-3, CD-19, CD-20, CD-22, CD-30, CD-33, CD-38, CD-40, CD-51, CD-52, CD-56, CD-70, CD-74, CD-79b, CD-138, CD-221, CD-319, CD-326, cell adhesion molecule 5, CTLA-4, cytokeratin polypeptides, death receptor 2, DLL4, EGFL7, EGFR, endosialin, EpCAM, FAP, FR-alpha, fibronectin, frizzled receptors, GD2, GPNMB, HER-1, HER-2, HER-3, IGF-IR, IGLF2, LOXL2, mesothelin, MS4A1, mucin 5AC, MUC1, Nectin-4, neuropilin, N-glycolyl GM3, PS
- Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the cancer cells having the antigen specific for the antibodies or binding fragments thereof.
- Administration may be by intravenous administration.
- An antibody or binding fragment thereof that specifically binds a pathogen may include an antibody or binding fragment thereof that binds a viral antigen on a virus or that binds a bacterial antigen on a bacterial cell.
- Antibodies that bind a viral antigen may include, for example, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, or umavizumab or a derivative, analogue, or binding fragment thereof.
- Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the virus having the antigen specific for the antibodies or binding fragments thereof.
- Administration may be by intravenous administration.
- Antibodies that bind a bacterial antigen, which can be conjugated with target moieties may include, for example, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a derivative, analogue, or binding fragment thereof.
- Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the bacterial cells having the antigen specific for the antibodies or binding fragments thereof.
- Administration may be by intravenous administration.
- Additional pathogenic antibodies which can be conjugated with target moieties, may include actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the pathogen having the antigen specific for the antibodies or binding fragments thereof.
- Administration may be by intravenous administration.
- any of the pathogenic specific antibodies or binding fragments thereof, which can be conjugated with target moieties may bind specifically to a viral antigen or a bacterial antigen, including, for example by binding to an antigen of a Bacillus, a Candida, a Clostridium, a cytomegalovirus, an Ebola virus, an Escherichia, a Gram-negative bacteria, a Gram-positive bacteria, a hepatitis virus, a herpes virus, an HIV, an influenza virus, a Pseudomonas, a Staphylococcus, or a syncytial virus.
- a viral antigen or a bacterial antigen including, for example by binding to an antigen of a Bacillus, a Candida, a Clostridium, a cytomegalovirus, an Ebola virus, an Escherichia, a Gram-negative bacteria, a Gram-positive bacteria, a hepatitis virus, a herpes virus, an HIV
- Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the pathogen having the antigen specific for the antibodies or binding fragments thereof.
- Administration may be by intravenous administration.
- the target moiety may include, for example, a a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, a digoxigenin, a dinotrophenol or a fluorescein.
- the target moiety is fluorescein isothiocyanate (FITC). Accordingly, the CAR described herein may bind to the target moiety on the antibody, thereby binding the cancer cell or pathogenic cell through the labeled antibody or fragment thereof.
- the spacer for a chimeric antigen receptor refers to a polypeptide spacer, wherein the length of the spacer is selected to increase or improve the ability of the chimeric antigen receptor to bind its target.
- the lipid can also comprise a spacer that separates the target moiety from the lipid and is bound to the polar-head group of the lipid.
- Selected polypeptide spacers for use with chimeric antigen receptors may be screened so as to identify a specific spacer, which promotes a desired binding characteristic to a target moiety (e.g., a desired receptor interaction or a desired avidity with the receptor).
- the spacer of the lipid can comprise a poly(carboxybetaine), peptide, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, PEG spacer, a Hapten spacer, a small peptide or an alkane chain.
- the hapten spacer comprises two haptens and is referred to as a hapten (2X) spacer.
- the hapten spacer comprises three haptens and is referred to as a hapten (3X) spacer.
- the hapten spacer comprises four haptens and is referred to as a hapten (4X) spacer. In some alternatives, the hapten spacer comprises five haptens and is referred to as a hapten (5X) spacer. In some alternatives, the hapten spacer comprises two, three, four or five different haptens.
- the lipid comprises a hydrophobic group, such as an alkane chain. In some alternatives, the alkane chain can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons, or any number of carbons in between a range defined by any two aforementioned values. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- “Hapten” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a small molecule binding moiety, which can be substituted for an scFvT or antibody.
- the three key advantages are that it is designed to (i) not trigger an immune response or a significantly diminished immune response, (ii) bind targets which may or may not be proteins or peptides or may be difficult to create a antibody/scFv binding moiety; and (iii) that it can be better optimized for binding/affinity.
- the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-tria
- DDT Metabolites p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N
- the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)(OH
- the cells provided are cytotoxic T lymphocytes.
- “Cytotoxic T lymphocyte” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a T lymphocyte that expresses CD8 on the surface thereof (e.g., a CD8 + T cell).
- such cells are preferably “memory” T cells (T M cells) that are antigen-experienced.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- “Masking moiety” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a moiety on the lipid ether that is bound to the target moiety.
- the masking moiety functions as a protective group to prevent recognition of the lipid’s target moiety by blocking binding and recognition of a chimeric antigen receptor that is specific for the target moiety.
- the masking moiety can be self-cleaved, thus allowing binding and recognition of the target moiety by the chimeric antigen receptor.
- the lipid is a phospholipid ether.
- the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the phospholipid ether comprises a target moiety and the CAR is joined to said phospholipid ether through an interaction with said target moiety.
- the phospholipid ether comprises a polar-head group and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- Cancer has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.
- Subjects that can be addressed using the methods described herein include subjects identified or selected as having cancer, including but not limited to colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, and brain cancer, etc. Such identification and/or selection can be made by clinical or diagnostic evaluation.
- the tumor associated antigens or molecules are known, such as melanoma, breast cancer, brain cancer, squamous cell carcinoma, colon cancer, leukemia, myeloma, and/or prostate cancer.
- Examples include but are not limited to B cell lymphoma, breast cancer, brain cancer, prostate cancer, and/or leukemia.
- one or more oncogenic polypeptides are associated with kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia.
- a method of treating, ameliorating, or inhibiting a cancer in a subject is provided.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the subject is selected to receive an additional cancer therapy, which can include a cancer therapeutic, radiation, chemotherapy, or a drug for the treatment of cancer.
- the drugs comprise Abiraterone, Alemtuzumab, Anastrozole, Aprepitant, Arsenic trioxide, Atezolizumab, Azacitidine, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Carboplatin, Cetuximab, Chemotherapy drug combinations, Cisplatin, Crizotinib, Cyclophosphamide, Cytarabine,Denosumab, Docetaxel, Doxorubicin, Eribulin, Erlotinib, Etoposide, Everolimus, Exemestane, Filgrastim, Fluorouracil, Fulvestrant, Gemcitabine, Imatinib, Imiquimod, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Letrozole, Leuprolide, Mesna, Methotrexate, Nivolumab, Oxa
- Tumor microenvironment has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a cellular environment, wherein a tumor exists.
- the tumor microenvironment can include surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules and/or the extracellular matrix (ECM).
- ECM extracellular matrix
- Described herein are synthetic molecular structures that are designed to decorate or label cancer cell membranes, such as tumor cell membranes. These synthetic structures contain recognition moieties that interact specifically with CAR T cells that are designed to target these recognition moieties.
- the molecular domains of phospholipid ether (PLE) CAR T cell tumor targeting (PLE-CTCT’s) agents comprise a cell membrane integrating domain composed of a lipid housing a polar-head group.
- the lipid is a phospholipid ether.
- the polar-head group can comprise of a phosphocholine and the carbon alkyl chain can comprise a preferred length of 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons, preferably 18 carbons.
- the lipid (PLE) when administered may also target tumor and cancer cells.
- the lipid (PLE) may be administered intravaneously.
- an extracellular extension from the polar-head group is conceived to be composed of a spacer and a molecular structure to which a CAR binds to at affinities that induce a CAR-expressing effector cell, preferably a T cell, activation signaling.
- the CAR recognition moiety of the PLE-CTCT is chemically modified such that the target moiety is masked from CAR recognition until it is chemically modified or unmasked by the tumor cell, tumor microenvironment (e.g., proteases present in the tumor microenvironment) or the tumor’s milieu.
- the target moiety is fluorescein and the masking modification comprising a phenolic hydroxy group, is introduced to a hydroxyl on the xanthene moiety of the fluorescein molecule.
- the masking modification is removed from the fluorescein in a reactive oxygen species (ROS) reaction, which can occur in a tumor microenvironment.
- ROS reactive oxygen species
- masking elements are conceived that become unmasked by hydrolysis that is dependent on ROS, low pH, hypoxia, nitrosylation, protease digestion, and other chemical reactions taking place in the tumor microenvironment.
- the unmasking is due to hydrolysis that is dependent on ROS, low pH, hypoxia, or nitrosylation within a tumor microenvironment.
- human tumor therapy is conceived in which patients receive infusions of PLE-CTCT’s in combination with infusions of PLE-CTCT specific CAR T cells.
- the PLE-CTCT when administered, may also target tumor and cancer cells. Administration may be by intravenous administration.
- this system represents a universal target antigen used in combination with a universal CAR and/or universal CAR expressing anti-tumor effector cell.
- a PLE (18C alkyl chain) having a fluorescein (FL) appended CAR recognition element appended to the polar-head group’s choline via PEG spacers was synthesized for use in the alternatives described herein. It was demonstrated that FL-specific scFv CAR T cells exhibit a redirected antitumor function in vitro and in vivo to tumors loaded with FL PLE-CTCT’s. Moreover, a FL PLE-CTCT housing a ROS responsive mask, is described in an exemplary alternative herein for further specification of targeting agent to tumor cells with active ROS microenvironments.
- Autologous T cells can be genetically modified to express transgenes that are engineered to enhance efficacy after transfer in vivo.
- transgene modified T cells in the setting of CD19 B cell lineage malignancies, no universal CAR target antigen that is present on all forms of cancer but not normal cells has been identified.
- the field is hampered by the need to identify cell surface targets that are naturally present on tumor cells and minimally expressed by normal cells/tissues of the body.
- CAR T cell therapeutic development is hampered by the prospect of potentially needing tens to hundreds of vetted CAR targets and CARs to cover the majority of cancer types afflicting humans.
- PLE-CTCT a synthetic exogenously delivered molecular construct that A) integrates into all cellular membranes of cancer cells (e.g., tumor cells) but is selectively rapidly catabolized by normal cells relative to tumor cells, and B) is equipped with masking elements that selectively “unmask” on tumor cells, provides for a “universal target” for CAR T cell immunotherapy, wherein the CAR is specific to the unmasked target moiety of the PLE-CTCT.
- the PLE’s as described herein, have the capacity for differential slow tumor membrane clearance compared to normal cell rapid clearance. These PLE’s have been conceived to carry imaging and radiotherapeutic payloads by modification to the alkyl chain of the PLE, which is buried within the lipid bilayers. As described in some alternatives herein, the target moieties were chemically built out from the PLE’s polar-head group to present the target moieties to CAR effector cells that would necessarily have to occur on the extracellular side of the tumor cell’s plasma membrane.
- cancer therapy can include surgery, targeted drug delivery, chemotherapy and radiation.
- approaches to cancer therapy have only limited effectiveness.
- radiation therapy is a tool often used to treat cancer in an attempt to improve local tumor control
- a key challenge is the limitation of dose escalation due to toxicity of neighboring sensitive normal organs.
- one critical problem with many cancer treatments is that despite initial responses, cancers become resistant to conventional therapies, and the cells that persist after treatment drive disease relapse.
- the methods provided herein can be used with and without these additional anti-cancer therapies so as to specifically target drug resistant residual disease or cancers.
- FIGS. 1 A and 1 B Examples of lipid CAR T cell tumor targeting agents are shown in FIGS. 1 A and 1 B .
- FL-PLE (1A) and ProFL-PLE (1B) FL-PLE (1A) and ProFL-PLE (1B).
- FL fluorescein
- PEG Polyetheneglycol
- PLE iii is the polar head group
- iv is the hydrophobic tail for incorporation or tethering into the cell plasma membrane.
- Masking moiety to prevent anti-FLCAR T cell recognition.
- ROS reactive oxygen species
- the lipid CAR T cell tumor targeting (CTCT) agents integrate into the membrane as shown in FIG. 2 .
- the CTCT agent is preferential for a tumor cell, or a tumor cell membrane.
- the CTCT agent can embed into a lipid raft on the cell membrane of a tumor cell and the masking moiety can be removed inside a ROS rich tumor microenvironment so that recognition and interaction with the specific CAR T cells can take place.
- lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid is a phospholipid ether.
- the lipid may target a tumor or a cancer cell or tumor or cancer cell membrane.
- the chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety.
- the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the PLE) and the transmembrane domain of the chimeric receptor.
- the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths.
- a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids.
- the spacer is optimized or selected to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety.
- the CAR comprises a co-stimulatory domain.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as an aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises at least 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid further comprises a spacer that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell.
- the target cell exists in a tumor microenvironment.
- the complex comprises a chimeric antigen receptor (CAR) joined to an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a target moiety and the CAR is joined to said antibody or fragment thereof through an interaction with said target moiety.
- CAR chimeric antigen receptor
- chimeric antigen receptor CAR
- TCR chimeric antigen receptor
- the targeting peptide targets a tumor cell or a cancer cell
- the targeting peptide comprises a target moiety and the CAR is joined to said peptide through an interaction with said target moiety.
- the chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety.
- the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the targeting peptide and the transmembrane domain of the chimeric receptor.
- the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths.
- a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids.
- the spacer is optimized or selected to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety.
- the CAR comprises a co-stimulatory domain.
- the targeting peptide comprises hydrophobic amino acids for integrating into the membrane of the target cell (e.g., a tumor cell or cancer cell).
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the targeting peptide further comprises a spacer that separates the target moiety from the polar head group.
- the spacer comprises a poly(carboxybetaine), a peptide spacer, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the CAR or TCR is expressed by a cell or a T cell.
- the CAR or TCR is on the surface of a cell or a T cell.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the targeting peptide is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell.
- the target cell exists in a tumor microenvironment.
- the complex comprises a chimeric antigen receptor (CAR) joined to an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a target moiety and the CAR is joined to said antibody or fragment thereof through an interaction with said target moiety.
- CAR chimeric antigen receptor
- lipid comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid.
- the lipid is a phospholipid ether.
- the chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety.
- the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the PLE) and the transmembrane domain of the chimeric receptor.
- the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths.
- a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids.
- the spacer is optimized to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety.
- the CAR comprises a co-stimulatory domain.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid further comprises a spacer group that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell.
- the target cell exists in a tumor microenvironment.
- CAR chimeric antigen receptor
- TCR T cell receptor
- chimeric antigen receptor CAR
- TCR T cell receptor
- the targeting peptide targets a tumor or cancer cell
- the targeting peptide comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid.
- the chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety.
- the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the PLE) and the transmembrane domain of the chimeric receptor.
- the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths.
- a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids.
- the spacer is optimized to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety.
- the CAR comprises a co-stimulatory domain.
- the lipid comprises a polar head group and a hydrophobic group.
- targeting peptide comprises hydrophobic amino acids.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the targeting peptide further comprises a spacer group that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment.
- CAR chimeric antigen receptor
- TCR T cell receptor
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprises a) introducing, providing, or administering to a subject a composition that comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor, which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to and/or interact with the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- the lipid is a phospholipid ether.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as an aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- Administration of the composition and the CAR T cell may be by intravenous administration.
- the hydrophobic group comprises a carbon alkyl chain.
- the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the masking moiety comprises a phenolic hydroxyl group or PEG.
- the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein.
- the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment.
- the cleavable moiety, which is configured to be cleavable in a tumor microenvironment is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the cell is provided to the subject the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36, 48, 60 or 72 hours after administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36 or 48 hours before administration of the composition, or any time within a range defined by any two aforementioned values.
- Administration of the composition and the CAR T cell may be by intravenous administration. In some alternatives, the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject. In some alternatives, a boost of the cell and/or the composition is provided to the subject.
- an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cell comprising the CAR or TCR is a T cell. In some alternatives, the CAR or TCR is on the surface of the cell or the T cell.
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid intercalates in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment. In some alternatives, a boost of the cell and/or the composition is provided to the subject. In some alternatives, free or freely available target moiety, such as fluorescein is provided to the subject so as to quench the therapy being provided. In some alternatives, an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- a small molecule e.g., a chemical compound
- an antibody therapy e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the subject is selected to receipt additional cancer therapy, which can include cancer therapeutics or drugs for the treatment of cancer.
- the drugs comprise Abiraterone, Alemtuzumab, Anastrozole, Aprepitant, Arsenic trioxide, Atezolizumab, Azacitidine, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Carboplatin, Cetuximab, Chemotherapy drug combinations, Cisplatin, Crizotinib, Cyclophosphamide, Cytarabine,Denosumab, Docetaxel, Doxorubicin, Eribulin, Erlotinib, Etoposide, Everolimus, Exemestane, Filgrastim, Fluorouracil, Fulvestrant, Gemcitabine, Imatinib, Imiquimod, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Letrozole, Leuprolide, Mesna, Methotrexate, Nivolumab, Oxa
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- a method comprising a) introducing, providing, or administering to a subject a composition that comprises an antibody or binding fragment thereof, which comprises a target moiety, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR), such as a T cell, which is specific for the target moiety, and, c) optionally, measuring or evaluating the binding of the cell comprising the CAR to the antibody or fragment thereof, after steps a-c and/or d) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-b, and/or e) optionally, identifying a subject in need of a therapy for cancer prior to steps a-b.
- CAR chimeric antigen receptor
- the antibody or binding fragment thereof comprising a target moiety is an antibody or binding fragment thereof specific to a cancer cell or a pathogenic cell. In some embodiments, the antibody or binding fragment thereof comprising the target moiety is specific to a tumor cell.
- Administration of the composition and the CAR T cell may be by intravenous administration.
- the antibody or binding fragment thereof comprising the target moiety includes abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab
- the antibody or binding fragment thereof, which comprises the target moiety includes cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, or umavizumab or a derivative, analogue, or binding fragment thereof.
- the antibody or binding fragment thereof includes, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a derivative, analogue, or binding fragment thereof.
- the antibody or binding fragment thereof includes actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprises a) introducing, providing, or administering to a subject a composition that comprises a targeting peptide, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor, which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to and/or interact with the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the targeting peptide, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally
- targeting peptide comprises hydrophobic amino acids.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the targeting peptide comprises a spacer for the targeting moiety.
- the spacer comprises a poly(carboxybetaine), peptide, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the masking moiety comprises a phenolic hydroxyl group or PEG.
- the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein.
- the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment.
- the cleavable moiety, which is configured to be cleavable in a tumor microenvironment is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the cell is provided to the subject the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36, 48, 60 or 72 hours after administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36 or 48 hours before administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject. In some alternatives, a boost of the cell and/or the composition is provided to the subject.
- an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cell comprising the CAR or TCR is a T cell. In some alternatives, the CAR or TCR is on the surface of the cell or the T cell.
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the targeting peptide intercalates in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment. In some alternatives, a boost of the cell and/or the composition is provided to the subject. In some alternatives, free or freely available target moiety, such as fluorescein is provided to the subject so as to quench the therapy being provided. In some alternatives, an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- a small molecule e.g., a chemical compound
- an antibody therapy e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the subject is selected to receipt additional cancer therapy, which can include cancer therapeutics or drugs for the treatment of cancer.
- the drugs comprise Abiraterone, Alemtuzumab, Anastrozole, Aprepitant, Arsenic trioxide, Atezolizumab, Azacitidine, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Carboplatin, Cetuximab, Chemotherapy drug combinations, Cisplatin, Crizotinib, Cyclophosphamide, Cytarabine,Denosumab, Docetaxel, Doxorubicin, Eribulin, Erlotinib, Etoposide, Everolimus, Exemestane, Filgrastim, Fluorouracil, Fulvestrant, Gemcitabine, Imatinib, Imiquimod, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Letrozole, Leuprolide, Mesna, Methotrexate, Nivolumab, Oxa
- a method comprising a) introducing, providing, or administering to a subject a composition that comprises an antibody or binding fragment thereof, which comprises a target moiety, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR), such as a T cell, which is specific for the target moiety, and, c) optionally, measuring or evaluating the binding of the cell comprising the CAR to the antibody or fragment thereof, after steps a-c and/or d) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-b, and/or e) optionally, identifying a subject in need of a therapy for cancer prior to steps a-b.
- CAR chimeric antigen receptor
- the antibody or binding fragment thereof comprising a target moiety is an antibody or binding fragment thereof specific to a cancer cell or a pathogenic cell. In some embodiments, the antibody or binding fragment thereof comprising the target moiety is specific to a tumor cell. In some embodiments, the antibody or binding fragment thereof comprising the target moiety includes abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab
- the antibody or binding fragment thereof, which comprises the target moiety includes cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, or umavizumab or a derivative, analogue, or binding fragment thereof.
- the antibody or binding fragment thereof includes, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a derivative, analogue, or binding fragment thereof.
- the antibody or binding fragment thereof includes actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- the binding site of the chimeric antigen receptor is designed so as to bind and/or interact with a target moiety of the FL-PLE.
- the targeting moiety may be a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the CAR comprises an antibody or antibody fragment, ScFv or a protein or portion thereof that is designed to recognize the target moiety.
- Designing proteins for interactions are known to those skilled in the art, and are desirably very specific, as proteins can interact with a large number of proteins or chemicals such as FL, for example, thus successful design should utilize selective binders.
- protein design algorithms can be used to distinguish between on target and off target binding.
- the protein can also be designed by focusing on electrostatic contributions, so as to increase the affinity for its binding partner, or target moiety. Screening of a variety of different CAR structures can be performed by contacting cells comprising CARs, which are specific for a target moiety, with a substrate or binding agent comprising said target moiety and evaluating the binding of the CARs to said substrate or binding agent.
- a target cell or a target virus unto which the binding agent is specific can be added so that the formation of a complex comprising the cell, which comprises the CAR, bound to the binding agent by virtue of the interaction of the CAR and the target moiety, and a target cell or virus unto which the binding agent is specific for can be evaluated.
- the scFv is specific for the FL-PLE.
- increasing the binding affinity of a CAR does not always increase the effects that one would expect for a high affinity binding CAR.
- the binding site of the chimeric antigen receptor is designed so as to bind and/or interact with a target moiety of the targeting peptide.
- the targeting moiety may be a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the CAR comprises an antibody or antibody fragment, ScFv or a protein or portion thereof that is designed to recognize the target moiety.
- Designing proteins for interactions are known to those skilled in the art, and are desirably very specific, as proteins can interact with a large number of proteins or chemicals such as FL, for example, thus successful design should utilize selective binders.
- protein design algorithms can be used to distinguish between on target and off target binding.
- the protein can also be designed by focusing on electrostatic contributions, so as to increase the affinity for its binding partner, or target moiety. Screening of a variety of different CAR structures can be performed by contacting cells comprising CARs, which are specific for a target moiety, with a substrate or binding agent comprising said target moiety and evaluating the binding of the CARs to said substrate or binding agent.
- a target cell or a target virus unto which the binding agent is specific can be added so that the formation of a complex comprising the cell, which comprises the CAR, bound to the binding agent by virtue of the interaction of the CAR and the target moiety, and a target cell or virus unto which the binding agent is specific for can be evaluated.
- the scFv is specific for the FL-PLE.
- increasing the binding affinity of a CAR does not always increase the effects that one would expect for a high affinity binding CAR.
- mice that can be used for these evaluations include mice with mutations in the MSH2 and/or MLH1 genes. These mice are susceptible to developing gastrointestinal cancer and tumors that are classified as adenomas, invasive adenocarcinomas and late stage carcinomas.
- mice In order to test for the efficacy of the compositions and CAR T cells expressing CARs that are specific for the target moiety, several groups of mice are selected for the study: 1) Control mice; 2) Mice given the FL-PLE; 3) Mice given the CAR T cell; 4) Mice given the FL-PLE followed by the CAR T cell 1 hour after FL-PLE administration; 5) Mice given the FL-PLE followed by the CAR T cell 2 hours after FL-PLE administration; 6) Mice given the FL-PLE followed by the CAR T cell 4 hours after FL-PLE administration; 7) Mice given the FL-PLE followed by the CAR T cell 6 hours after FL-PLE administration; 8) Mice given the FL-PLE followed by the CAR T cell 12 hours after FL-PLE administration; 9) Mice given the FL-PLE followed by the CAR T cell 24 hours after FL-PLE administration; and 10) Mice given the FL-PLE followed by the CAR T cell 48 hours after FL-PLE administration.
- Administration of the composition and the CAR T cell may be by intravenous administration.
- Each group of the mice have mutations in the MSH2 and MLH1 genes and have early stage tumors as detected by diffusion weighted whole body imaging.
- Each group of mice have 5 males and 5 females aged 16 weeks. Experiments were also performed where tumors are engrafted at day 0 and days 5-7.
- FL-PLEs are injected for integration into cells and this is followed by T cells injected on day 7.
- FL-PLE’s may then be redosed weekly or bi weekly.
- the tumors are again analyzed for size by diffusion weighted whole body imaging to review the sizes of the tumors in the mice. It is expected that the mice that were administered the FL-PLE followed by the CAR T cell will have an appreciable reduction and/or inhibition of tumor growth.
- FIG. 3 Shown in FIG. 3 is the synthesis of a FL-PLE.
- the synthesized FL-PLE was subjected to an NMR analysis.
- a 1D NMR spectra was obtained with the FL-PLE sample in a buffer solution ( FIG. 4 ).
- the 1D spectra of the sample of the synthesized FL-PLE indicated peaks for the specific groups on the molecule which were expected for the synthesized structure of the FL-PLE.
- FIG. 5 Shown in FIG. 5 , is the synthesis scheme for ProFL-PLE.
- a 1D NMR spectra was obtained with the ProFL-PLE sample in a buffer solution ( FIG. 6 ).
- the 1D spectra of the sample of the synthesized ProFL-PLE indicated peaks for the specific groups on the molecule which were expected for the synthesized structure of the ProFL-PLE.
- FIG. 7 A shows FL-PLE is able to integrate into multiple cancers: Be2 (neuroblastoma), U87 (glioblastoma), and daoy (medulloblastoma).
- FIGS. 7 B U 87 cells were incubated overnight in the presence of 0, 0.1, 1, or 5 ⁇ M FL-PLE and then subjected to flow analysis. The results demonstrate that FL-PLE integration into the cancer cell membrane is concentration dependent.
- FIG. 9 A Cell integration of FL-PLE was analyzed by flow cytometry ( FIG. 9 A ). There is a clear shift from the control K562 parental with the K562 parental incubated with 5 ⁇ M FL-PLE; whereas there is a very slight shift with K562 parental incubated with 0.5 ⁇ M FL-PLE. This slight shift corresponds to a difference in the amount of FL exposed on the surface of the cell for CAR T cell recognition. Also, the K562+OKT3 cells (a cell line created to test the endogenous activation of T cells through the TCR) match the K562 parental exactly, as expected. These cells were used in a chromium release assay ( FIG. 9 B ) and a cytokine release assay ( FIG.
- Shown in FIG. 12 is an example of a construction scheme for the synthesis of fluorescein-PEG-phosphatidylcholine.
- Shown in FIG. 13 is an example of a construction scheme for the synthesis of fluorescein-PEG.
- Shown in FIG. 14 is an example of a construction scheme for ProFL-NHS.
- the target cell is a cancer cell such as a tumor cell.
- the target cell is an immune cell.
- the target cell is in a tumor microenvironment.
- the target cell is a tumor cell of a solid tumor.
- the solid tumor is a cancerous tumor, wherein the tumor comprises a plurality of cancer cells.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic moiety.
- the hydrophobic moiety is a hydrophobic carbon tail.
- the hydrophobic carbon tail is saturated or unsaturated.
- the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value.
- the hydrophobic moiety is a steroid or a cholesterol or comprises an aromatic ring.
- the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide.
- the lipid is a phospholipid ether.
- the lipid contains branched alkyl tails.
- the lipid can be a sphingolipid.
- the sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine.
- a sphingolipid with an R group consisting of a hydrogen atom only is a ceramide.
- Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
- the lipid is a glycosphingolipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group comprises a fatty acid such as an aliphatic chain. The fatty acid can be saturated or unsaturated depending on the desired embodiments.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or comprises an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the lipid is a single chain alkylphospholipid.
- the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine.
- the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine.
- lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- a choline within the polar head group can be substituted with a piperidine moiety.
- the lipid is an anticancer alkylphospholipid.
- Anticancer phospholipids are described e.g., in vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein).
- the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and/or Erufosine.
- the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine.
- the lipid is a stable analog of lysophosphatidylcholine.
- the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine.
- the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid is a phospholipid ether.
- the phospholipid ether comprises a polar-head group and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- a complex is provided, wherein the complex comprises a lipid.
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- the lipid comprises a polar head group.
- the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid is a phospholipid ether.
- the sugar is a glycerol.
- the polar head group of the lipid comprises glycerol.
- the polar head group of the lipid comprises a phosphate group.
- the polar head group of the lipid comprises choline.
- the lipid is a phosphatidylethanolomine.
- the lipid is a phosphatidylinositol.
- the lipid comprises a sphingoid base backbone.
- the lipid comprises a sterol lipid, such as cholesterol or its derivatives.
- the lipid comprises saccharolipids.
- the polar head group comprises choline, phosphate and/or glycerol.
- the lipid is a glycolipid.
- the lipid comprise a sugar.
- the lipid is derived from sphingosine.
- the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR.
- the lipid can comprise a spacer that separates the target moiety from the lipid and is bound to the polar-head group of the lipid.
- the spacer of the lipid can comprise a poly(carboxybetaine), peptide, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the hapten spacer comprises two haptens and is referred to as a hapten (2X) spacer.
- the lipid comprises a hydrophobic group such as an alkane chain.
- the alkane chain can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons, or any number of carbons in between a range defined by any two aforementioned values.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the spacer comprises at least two haptens, at least three haptens or at least four haptens.
- the FL-PLE comprises multiple fluoresceins.
- the FL-PLE comprises 1, 2, 3, 4 or 5 flourescein moieties.
- a target cell is a cancer cell or a pathogenic cell.
- the target cell is a tumor cell.
- the target cell is a tumor cell of a solid tumor.
- the solid tumor is a cancerous tumor, wherein the tumor comprises a plurality of cancer cells.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the target cell is a virus or a bacteria.
- the antibody is a full antibody or a binding fragment thereof that specifically binds to an antigen on a target cell.
- the antigen is an angiopoietin, a transmembrane receptor, a cell adhesion molecule, a cluster of differentiation molecule, a ganglioside, a glycoprotein, a growth factor, an integrin, an interleukin, a Notch receptor, a transmembrane glycoprotein, a tumor necrosis factor, or a tyrosine kinase.
- antigen is 5T4, B7-H3, carbonic anhydrase IX, carcinoembryonic antigen, CA-125, CD-3, CD-19, CD-20, CD-22, CD-30, CD-33, CD-38, CD-40, CD-51, CD-52, CD-56, CD-70, CD-74, CD-79b, CD-138, CD-221, CD-319, CD-326, cell adhesion molecule 5, CTLA-4, cytokeratin polypeptides, death receptor 2, DLL4, EGFL7, EGFR, endosialin, EpCAM, FAP, FR-alpha, fibronectin, frizzled receptors, GD2, GPNMB, HER-1, HER-2, HER-3, IGF-IR, IGLF2, LOXL2, mesothelin, MS4A1, mucin 5AC, MUC1, Nectin-4, neuropilin, N-glycolyl GM3, PSMA, SLAMF7, TAG
- the antibody or binding fragment, which is conjugated with a target moiety, thereof may bind specifically to a viral antigen or a bacterial antigen, including, for example by binding to an antigen of a Bacillus, a Candida, a Clostridium, a cytomegalovirus, an Ebola virus, an Escherichia, a Gram-negative bacteria, a Gram-positive bacteria, a hepatitis virus, a herpes virus, an HIV, an influenza virus, a Pseudomonas, a Staphylococcus, or a syncytial virus.
- an antibody or fragment thereof may bind to a core antigen of HBV or HCV.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to an antibody or binding fragment thereof, wherein the antibody or binding fragment thereof comprises a target moiety and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety.
- CAR chimeric antigen receptor
- TCR T cell receptor
- the antibody or binding fragment thereof which comprises a target moiety, comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzum
- the antibody or binding fragment thereof comprises a target moiety and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety. In some alternatives, the antibody or binding fragment thereof further comprises a target moiety, which interacts with the CAR or TCR.
- kits that comprises a pharmaceutical grade PLE-CTCT, which can be used with a CAR T cell product designed to be specific for a recognition moiety on said PLE-CEC in the tumor or cancer.
- kits that comprises an antibody or binding fragment thereof labeled with a target moiety, which can be used with a CAR T cell product designed to be specific for a recognition moiety on said labeled antibody or binding fragment thereof.
- the antibody or binding fragment thereof, which comprises the target moiety comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzuma
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as an aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 18 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid further comprises a spacer that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the CAR or TCR is expressed by a cell or a T cell.
- the CAR or TCR is on the surface of a cell or a T cell.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor is from a cancer.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic moiety.
- the hydrophobic moiety is a hydrophobic carbon tail.
- the hydrophobic carbon tail is saturated or unsaturated.
- the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value.
- the hydrophobic moiety is a steroid or a cholesterol.
- the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide.
- the lipid is a phospholipid ether.
- the lipid contains branched alkyl tails.
- the lipid can be a sphingolipid.
- the sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine.
- a sphingolipid with an R group consisting of a hydrogen atom only is a ceramide.
- Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
- the lipid is a glycosphingolipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group comprises a fatty acid such as an aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the lipid is a single chain alkylphospholipid.
- the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine.
- the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine.
- Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- a choline within the polar head group can be substituted with a piperidine moiety.
- the lipid is an anticancer alkylphospholipid.
- Anticancer phospholipids are described by vander Lui et al.
- the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein).
- the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and/or Erufosine.
- the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine.
- the lipid is a stable analog of lysophosphatidylcholine.
- the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine.
- the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar-head group and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the lipid is a phospholipid ether.
- a complex is provided, wherein the complex comprises a lipid.
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- the lipid comprises a polar head group.
- the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid is a phospholipid ether.
- the sugar is a glycerol.
- the polar head group of the lipid comprises glycerol.
- the polar head group of the lipid comprises a phosphate group.
- the polar head group of the lipid comprises choline.
- the lipid is a phosphatidylethanolomine.
- the lipid is a phosphatidylinositol.
- the lipid comprises a sphingoid base backbone.
- the lipid comprises a sterol lipid, such as cholesterol or its derivatives.
- the lipid comprises saccharolipids.
- the polar head group comprises choline, phosphate and/or glycerol.
- the lipid is a glycolipid.
- the lipid comprise a sugar.
- the lipid is derived from sphingosine.
- the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR.
- the cancer is kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, and brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cancer is a neuroblastoma, glioblastoma, leukemia or medulloblastoma.
- an antibody or binding fragment thereof which comprises a target moiety, is used and such antibody or binding fragment thereof is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetm
- a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) is provided, wherein the CAR or TCR is bound to a lipid, wherein the lipid comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is a fatty acid such as an aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid further comprises a spacer group that separates the target moiety from the polar head group.
- the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor is from a cancer.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic moiety.
- the hydrophobic moiety is a hydrophobic carbon tail.
- the hydrophobic carbon tail is saturated or unsaturated.
- the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value.
- the hydrophobic moiety is a steroid or a cholesterol or comprises an aromatic ring.
- the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide.
- the lipid is a phospholipid ether.
- the lipid contains branched alkyl tails.
- the lipid can be a sphingolipid.
- the sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine.
- a sphingolipid with an R group consisting of a hydrogen atom only is a ceramide.
- Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
- the lipid is a glycosphingolipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group comprises a fatty acid such as an aliphatic chain. The fatty acid can be saturated or unsaturated depending on the desired embodiments.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the lipid is a single chain alkylphospholipid.
- the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine.
- the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine.
- Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- a choline within the polar head group can be substituted with a piperidine moiety.
- the lipid is an anticancer alkylphospholipid.
- Anticancer phospholipids are described by vander Lui et al.
- the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein).
- the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and/or Erufosine.
- the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine.
- the lipid is a stable analog of lysophosphatidylcholine.
- the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine.
- the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar-head group and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the lipid is a phospholipid ether.
- a complex is provided, wherein the complex comprises a lipid.
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- the lipid comprises a polar head group.
- the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid is a phospholipid ether.
- the sugar is a glycerol.
- the polar head group of the lipid comprises glycerol.
- the polar head group of the lipid comprises a phosphate group.
- the polar head group of the lipid comprises choline.
- the lipid is a phosphatidylethanolomine.
- the lipid is a phosphatidylinositol.
- the lipid comprises a sphingoid base backbone.
- the lipid comprises a sterol lipid, such as cholesterol or its derivatives.
- the lipid comprises saccharolipids.
- the polar head group comprises choline, phosphate and/or glycerol.
- the lipid is a glycolipid.
- the lipid comprises a sugar.
- the lipid is derived from sphingosine.
- the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR.
- the cancer is kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone cancer, brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- an antibody or binding fragment thereof conjugated to a target moiety is used and said antibody or binding fragment thereof can include abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuxim
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprising: a) introducing, providing, or administering to a subject a composition that comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally,
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as an aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain.
- the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the masking moiety comprises a phenolic hydroxyl group or PEG.
- the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein.
- the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment.
- the cleavable moiety which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- the cell is provided to the subject the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36, 48, 60 or 72 hours after administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36 or 48 hours before administration of the composition, or any time within a range defined by any two aforementioned values. In some alternatives, the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject. In some alternatives, a boost of the cell and/or the composition is provided to the subject.
- an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cell comprising the CAR or TCR is a T cell. In some alternatives, the CAR or TCR is on the surface of the cell or the T cell.
- the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid intercalates in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor is from a cancer.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic moiety.
- the hydrophobic moiety is a hydrophobic carbon tail.
- the hydrophobic carbon tail is saturated or unsaturated.
- the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value.
- the hydrophobic moiety is a steroid or a cholesterol or comprises an aromatic ring.
- the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide.
- the lipid is a phospholipid ether.
- the lipid contains branched alkyl tails.
- the lipid can be a sphingolipid.
- the sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine.
- a sphingolipid with an R group consisting of a hydrogen atom only is a ceramide.
- Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
- the lipid is a glycosphingolipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group comprises a fatty acid such as an aliphatic chain. The fatty acid is saturated or unsaturated depending on the desired embodiments.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the lipid is a single chain alkylphospholipid.
- the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine.
- the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine.
- lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- a choline within the polar head group can be substituted with a piperidine moiety.
- the lipid is an anticancer alkylphospholipid.
- Anticancer phospholipids are described by vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein).
- the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and Erufosine.
- the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine.
- the lipid is a stable analog of lysophosphatidylcholine.
- the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine.
- the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar-head group and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group. In some alternatives, the lipid is a phospholipid ether.
- the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid is a phospholipid ether.
- the sugar is a glycerol.
- the polar head group of the lipid comprises glycerol.
- the polar head group of the lipid comprises a phosphate group.
- the polar head group of the lipid comprises choline.
- the lipid is a phosphatidylethanolomine.
- the lipid is a phosphatidylinositol.
- the lipid comprises a sphingoid base backbone.
- the lipid comprises a sterol lipid, such as cholesterol or its derivatives.
- the lipid comprises saccharolipids.
- the polar head group comprises choline, phosphate and/or glycerol.
- the lipid is a glycolipid.
- the lipid comprises a sugar.
- the lipid is derived from sphingosine.
- the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR.
- the cancer is kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, and brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer..
- a method of treating, ameliorating, or inhibiting a cancer in a subject is provided.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the subject is selected to receipt additional cancer therapy which can include cancer therapeutics or drugs for the treatment of cancer.
- the drugs comprise Abiraterone, Alemtuzumab, Anastrozole, Aprepitant, Arsenic trioxide, Atezolizumab, Azacitidine, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Carboplatin, Cetuximab, Chemotherapy drug combinations, Cisplatin, Crizotinib, Cyclophosphamide, Cytarabine,Denosumab, Docetaxel, Doxorubicin, Eribulin, Erlotinib, Etoposide, Everolimus, Exemestane, Filgrastim, Fluorouracil, Fulvestrant, Gemcitabine, Imatinib, Imiquimod, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Letrozole, Leuprolide, Mesna, Methotrexate, Nivolumab, Oxa
- an antibody or binding fragment thereof is used and said antibody or binding fragment thereof can be abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictu
- a composition comprising a lipid, wherein the lipid comprises a target moiety that is bound to a masking moiety.
- the target is bound to the masking moiety through a spacer.
- the masking moiety is removed when the composition is in a tumor microenvironment.
- the masking moiety is removed when the composition is in a ROS rich tumor environment.
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- a method of treating, ameliorating, or inhibiting a cancer in a subject comprises a) introducing, providing, or administering to a subject the composition of any one of the alternatives herein, wherein the composition comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-
- CAR chimeric antigen receptor
- the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group is fatty acid such as a aliphatic chain.
- the fatty acid is saturated or unsaturated.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein.
- the hydrophobic group comprises a carbon alkyl chain.
- the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values.
- the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain.
- the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- the masking moiety comprises a phenolic hydroxyl group or PEG.
- the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein.
- the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment.
- the masking moiety is removed when the composition is within an acidic environment.
- the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values.
- the masking moiety is removed by nitrosylation.
- the cleavable moiety which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation.
- the cell is provided to the subject the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36, 48, 60 or 72 hours after administration of the composition, or any time within a range defined by any two aforementioned values.
- the cell is provided to the subject 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 24, 36 or 48 hours before administration of the composition, or any time within a range defined by any two aforementioned values.
- the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject.
- a boost of the cell and/or the composition is provided to the subject.
- an additional cancer therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer.
- the cell comprising the CAR or TCR is a T cell.
- the CAR or TCR is on the surface of the cell or the T cell.
- the cell is a precursor T cell.
- the precursor T cell is a hematopoietic stem cell.
- the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of na ⁇ ve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells.
- the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of na ⁇ ve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- the lipid intercalates in a lipid bilayer of a target cell, such as a cancer cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the target cell is a tumor cell.
- the target cell is an immune cell.
- the immune cell is a T cell or a B cell.
- the target cell is in a tumor microenvironment.
- the target cell is a tumor cell of a solid tumor.
- the solid tumor is a cancerous tumor, wherein the tumor is from a cancer.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide.
- a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar head group and a hydrophobic moiety.
- the hydrophobic moiety is a hydrophobic carbon tail.
- the hydrophobic carbon tail is saturated or unsaturated. In some alternatives, the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value. In some alternatives, the hydrophobic moiety is a steroid or a cholesterol or comprises an aromatic ring. In some alternatives, the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid contains branched alkyl tails.
- the lipid can be a sphingolipid.
- the sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine.
- a sphingolipid with an R group consisting of a hydrogen atom only is a ceramide.
- Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
- the lipid is a glycosphingolipid.
- the lipid comprises a polar head group and a hydrophobic group.
- the hydrophobic group comprises a fatty acid such as an aliphatic chain. The fatty acid is saturated or unsaturated depending on the desired embodiments.
- the hydrophobic group comprises an alkyl, alkenyl or alkynyl group.
- the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring.
- the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain.
- the lipid is a phospholipid ether.
- the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the sugar is a glycerol.
- the lipid is a single chain alkylphospholipid.
- the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine.
- the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine.
- lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- a choline within the polar head group can be substituted with a piperidine moiety.
- the lipid is an anticancer alkylphospholipid.
- Anticancer phospholipids are described by vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein).
- the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and Erufosine.
- the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine.
- the lipid is a stable analog of lysophosphatidylcholine.
- the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine.
- the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- the lipid comprises a polar-head group and a carbon alkyl chain.
- the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group. In some alternatives, the lipid is a phospholipid ether.
- the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol.
- the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety.
- the lipid is a phospholipid ether.
- the sugar is a glycerol.
- the polar head group of the lipid comprises glycerol.
- the polar head group of the lipid comprises a phosphate group.
- the polar head group of the lipid comprises choline.
- the lipid is a phosphatidylethanolomine.
- the lipid is a phosphatidylinositol.
- the lipid comprises a sphingoid base backbone.
- the lipid comprises a sterol lipid, such as cholesterol or its derivatives.
- the lipid comprises saccharolipids.
- the polar head group comprises choline, phosphate and/or glycerol.
- the lipid is a glycolipid.
- the lipid comprises a sugar.
- the lipid is derived from sphingosine.
- the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR.
- the cancer is kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, and brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer..
- a method of treating, ameliorating, or inhibiting a cancer in a subject is provided.
- the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer.
- the subject is selected to receipt additional cancer therapy which can include cancer therapeutics or drugs for the treatment of cancer.
- the drugs comprise Abiraterone, Alemtuzumab, Anastrozole, Aprepitant, Arsenic trioxide, Atezolizumab, Azacitidine, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Carboplatin, Cetuximab, Chemotherapy drug combinations, Cisplatin, Crizotinib, Cyclophosphamide, Cytarabine,Denosumab, Docetaxel, Doxorubicin, Eribulin, Erlotinib, Etoposide, Everolimus, Exemestane, Filgrastim, Fluorouracil, Fulvestrant, Gemcitabine, Imatinib, Imiquimod, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Letrozole, Leuprolide, Mesna, Methotrexate, Nivolumab, Oxa
- an antibody or binding fragment thereof which comprises a target moiety, is used and said antibody or binding fragment thereof comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuxim
- any of the features of an embodiment of the first through ninth aspects is applicable to all aspects and embodiments identified herein. Moreover, any of the features of an embodiment of the first through ninth aspects is independently combinable, partly or wholly with other embodiments described herein in any way, e.g., one, two, or three or more embodiments may be combinable in whole or in part. Further, any of the features of an embodiment of the first through ninth aspects may be made optional to other aspects or embodiments.
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Abstract
Aspects of the invention described herein relate to synthetic compounds that are useful for targeting and labeling tumor cells so as to facilitate recognition by binding agents including Chimeric Antigen Receptor T cells (CAR T cells), which are administered to a subject by intravenous or locoregional administration. Several compositions and methods of making and using these compositions to treat or inhibit a disease in a subject are contemplated.
Description
- This application is a division of U.S. App. No. 16/480,833 filed Jul. 25, 2019 which a U.S. National Phase Application of PCT International Application Number PCT/US2018/017126 filed on Feb. 6, 2018, designating the United States of America and published in the English language, which is an International Application of and claims the benefit of priority to U.S. Provisional Application No. 62/456,027, filed on Feb. 7, 2017. The disclosures of the above-referenced applications are hereby expressly incorporated by reference in their entireties.
- The alternatives described herein pertain to synthetic compounds that are designed to target and selectively decorate tumor cell membranes so as to facilitate recognition by binding agents. In some alternatives, the synthetic compounds have recognition moieties that interact with specific Chimeric Antigen Receptor T cells (CAR T cells), in which both the synthetic compounds and the CAR T cells are administered to a subject by intravenous or locoregional administration. Accordingly, several compositions and methods of making and using these compositions to treat or inhibit disease in a subject are contemplated.
- The adoptive transfer of human T lymphocytes that are engineered by gene transfer to express chimeric antigen receptors (CARs) specific for surface molecules expressed on tumor cells has the potential to effectively treat cancer. Chimeric receptors are synthetic receptors that include an extracellular ligand binding domain, most commonly a single chain variable fragment of a monoclonal antibody (scFv) linked to intracellular signaling components, most commonly CD3ζ alone or combined with one or more costimulatory domains. Much of the research in the design of chimeric receptors has focused on defining scFvs and other ligand binding elements that target malignant cells without causing serious toxicity to essential normal tissues, and on defining the optimal composition of intracellular signaling modules to activate T cell effector functions. There remains a need for a CAR T cell-mediated therapy that is selective for specific targets and which minimizes adverse side effects.
- In a first aspect, a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is a carbon chain or a fatty acid such as an aliphatic chain. In some alternatives, the carbon chain or fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or it comprises an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the hapten, which is a target moiety, comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene),, 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/Cl/C6 R1= NH2- R2= -Cl R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -Cl R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;,Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3’,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2’,4,4’,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-
Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB1089(Seocalcitol),EB 1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -C1 R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -Cl R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HClo1, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine in position 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HClo1 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2′,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-(3-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = C1 R3 = CN R4 = OH R5 = Cl R6 = Cl), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = COOH R4 = H R5 = Cl R6 = Cl), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = C1 R3 = Cl R4 = C1 R5 = Cl R6 = Cl), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = C1 R2 = C1 R3 = C1 R4 = Cl R5 = Cl R6 = Cl), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = C1 R3 = H R4 = Cl R5 = Cl R6 = C1 ), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,, HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners - 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3,4-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = C1 R2 = C1 R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = C1 R2 = C1 R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = C1 R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-
nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3’,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens. In some alternatives, the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid further comprises a spacer that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a Hapten (2x) spacer, a Hapten (3x) spacer, a Hapten (4x) spacer, a Hapten (5x) spacer, or an alkane chain. In some alternatives, the spacer comprises poly(carboxybetaine), peptides, polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone or Poly(ethylene oxide). In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment. - In a second aspect, a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) is provided, wherein the CAR or TCR is bound to a lipid, wherein the lipid comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is a carbon chain or a fatty acid such as an aliphatic chain. In some alternatives, the carbon chain or fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or it comprises an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid further comprises a spacer group that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a Hapten (2x) spacer, a Hapten (3x) spacer, a Hapten (4x) spacer, a Hapten (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment. In some alternatives, the hapten, which is a target moiety, comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/Cl/C6 R1= NH2- R2= -Cl R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -Cl R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3′,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2′,4,4′,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB1089(Seocalcitol),EB1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -C1 R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -Cl R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -C1 R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HClo1, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine in position 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HClo1 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2′,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-(3-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = C1 R3 = CN R4 = C1 R5 = C1 R6 = C1), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = CN R4 = C1 R5 = C1 R6 = C1), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = C1 R3 = CN R4 = OH R5 = C1 R6 = C1), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = COOH R4 = H R5 = C1 R6 = C1), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = C1 R3 = C1 R4 = C1 R5 = C1 R6 = C1), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = C1 R2 = C1 R3 = C1 R4 = C1 R5 = C1 R6 = C1), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = C1 R3 = H R4 = C1 R5 = C1 R6 = C1 ), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,,HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners
- 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3’,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = C1 R2 = C1 R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = C1 R2 = C1 R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = C1 R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3′,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In a third aspect, a method of treating, ameliorating, or inhibiting a cancer in a subject is provided, the method comprising: a) introducing, providing, or administering to a subject a composition that comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying a subject in need of a therapy for cancer prior to steps a-c. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as a carbon chain or an aliphatic chain. In some alternatives, the carbon chain or fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the spacer comprises a PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the cell is provided to the
subject subject - 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = C1 R2 = C1 R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = C1 R2 = C1 R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = C1 R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3′,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In a fourth aspect, a composition is provided, wherein the composition comprises a lipid, and wherein the lipid comprises a target moiety that is bound to a masking moiety. In some alternatives, the target is bound to the masking moiety through a spacer. In some alternatives, the masking moiety is removed when the composition is in a tumor microenvironment. In some alternatives, the masking moiety is removed when the composition is in a ROS rich tumor environment. In some alternatives, the masking moiety is removed when the composition is within an acidic environment. In some alternatives, the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values. In some alternatives, the masking moiety is removed by nitrosylation.
- In a fifth aspect, a method of treating, ameliorating, or inhibiting a cancer in a subject is provided, wherein the method comprises: a) introducing, providing, or administering to a subject the composition of any one of the alternatives herein, wherein the composition comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying a subject in need of a therapy for cancer prior to steps a-c. In some alternatives, the composition comprises a lipid, wherein the lipid comprises a target moiety that is bound to a masking moiety. In some alternatives, the target is bound to the masking moiety through a spacer. In some alternatives, the masking moiety is removed when the composition is in a tumor microenvironment. In some alternatives, the masking moiety is removed when the composition is in a ROS rich tumor environment. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether (PLE). In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 18 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the spacer comprises a PEG spacer, a Hapten (2x) spacer, a Hapten (3x) spacer, a Hapten (4x) spacer, a Hapten (5x) spacer,or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the cell is provided to the
subject subject - 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = C1 R2 = C1 R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = C1 R2 = C1 R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = C1 R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cy, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3′,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In a sixth aspect, a complex is provided, wherein the complex comprises a chimeric antigen receptor (CAR) or a T cell receptor (TCR), wherein the CAR or TCR is joined to a peptide (which, optionally, may comprise one or more haptens joined thereto, e.g., by way of covalent or disulfide bonds), an antibody or binding fragment thereof through a CAR or TCR-mediated interaction with said target moiety and, wherein said antibody or binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell. In some alternatives, said target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)). In some alternatives, the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives the peptide, which comprises a target moiety, such as fluorescin, is an albumin, a mutant albumin, or a fragment thereof, a cyclic peptide PEGA, or CREKA. In some alternatives, the antibody or binding fragment thereof, which comprises a target moiety, such as fluorescin, is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a binding fragment thereof. In some alternatives, the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/Cl/C6 R1= NH2- R2= -C1 R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -C1 R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;,Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3′,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2′,4,4′,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB 1089(Seocalcitol),EB 1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -C1 R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -C1 R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HClo1, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine in position 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HClo1 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2′,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-(3-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = OH R5 = Cl R6 = Cl), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = COOH R4 = H R5 = Cl R6 = Cl), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = Cl R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = Cl R3 = H R4 = Cl R5 = Cl R6 = Cl ), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,, HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners
- 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = Cl R2 = Cl R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = Cl R2 = Cl R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = Cl R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3′,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In a seventh aspect, a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) is provided, wherein the CAR or TCR is configured to bind with an antibody or binding fragment thereof comprising a target moiety through a CAR or TCR-mediated interaction with said target moiety and, wherein said antibody or binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell. In some alternatives, said target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein (e.g., Fluorescein isothiocyanate (FITC)). In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/Cl/C6 R1= NH2- R2= -C1 R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -C1 R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;,Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3′,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2′,4,4′,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB 1089(Seocalcitol),EB 1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -C1 R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -Cl R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HClo1, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine in position 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HClo1 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2′,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-(3-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = OH R5 = Cl R6 = Cl), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = COOH R4 = H R5 = Cl R6 = Cl), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = Cl R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = C1 R3 = H R4 = C1 R5 = Cl R6 = Cl), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,, HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners
- 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = C1 R2 = C1 R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = C1 R2 = C1 R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = C1 R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3′,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In an eighth aspect, a method of treating, ameliorating, or inhibiting a cancer in a subject is provided, wherein the method comprises a) introducing, providing, or administering to a subject a composition that comprises an antibody or binding fragment thereof, which comprises a target moiety such as, a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein (e.g., Fluorescein isothiocyanate (FITC)); and b) introducing, providing, or administering to said subject a cell that comprises a chimeric antigen receptor (CAR) or T cell receptor (TCR), wherein the CAR or TCR is specific for the target moiety. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the antibody or binding fragment thereof, which comprises the target moiety, is specific for a target or selected cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the target immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment. In some alternatives, the antibody or binding fragment thereof, which comprises the target moiety, is specific for a viral or bacterial antigen. In some alternatives, the cell comprises a chimeric antigen receptor (CAR) or T cell receptor (TCR), wherein the CAR or TCR is configured to bind with an antibody or binding fragment thereof comprising a target moiety through a CAR or TCR-mediated interaction with said target moiety and, wherein said antibody or binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell. In some alternatives, said target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein (e.g., Fluorescein isothiocyanate (FITC)). In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives of the method, the cell is provided to the subject within seconds or minutes, such as less than an hour, of providing the composition to the subject. In some alternatives of the method, a boost of the cell and/or the composition is provided to the subject. In some alternatives of the method, an additional therapy is provided, such as a small molecule, e.g., a chemical compound, an antibody therapy, e.g., a humanized monoclonal antibody with or without conjugation to a radionuclide, toxin, or drug, surgery, and/or radiation. In some alternatives, the antibody or binding fragment thereof, which is conjugated to the target moiety, is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a binding fragment thereof. In some alternatives, the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/Cl/C6 R1= NH2- R2= -Cl R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -Cl R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;,Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3′,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2′,4,4′,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB 1089(Seocalcitol),EB 1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -Cl R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -Cl R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -C1 R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HClo1, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine in position 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HClo1 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2′,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-(3-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = OH R5 = Cl R6 = Cl), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = COOH R4 = H R5 = Cl R6 = Cl), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = Cl R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = Cl R3 = H R4 = Cl R5 = Cl R6 = Cl), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = C1 R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,, HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners
- 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = Cl R2 = Cl R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = Cl R2 = Cl R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = Cl R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3’,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In a ninth aspect, a method of screening cells that comprise a CAR or TCR is provided, whereby cells, such as T cells, which comprise a CAR or TCR are evaluated for the ability to bind or interact with a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), which is present on a substrate, such as a membrane, bead, or support (e.g., a well) or a binding agent, such as a lipid (e.g., PLE), hapten, ligand, or antibody, or binding fragment thereof, preferably a binding agent that has specificity for an antigen present on a cancer cell or pathogen such as, a virus or bacteria. By one approach, the substrate or binding agent comprising the desired target moiety is contacted with a plurality of cells comprising a CAR or TCR specific for said target moiety and the level or amount of binding of the cells comprising the CAR or TCR to the target moiety present on the substrate or binding agent is determined. Such an evaluation of binding may include staining for cells bound to target moieties or evaluation of fluorescence or loss of fluorescence. In some approaches, a target cell is also provided such that the method comprises contacting a cell, such as a T cell, which comprises a CAR or TCR that is specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), with a binding agent such as a hapten, ligand, or antibody or antibody fragment thereof joined to said target moiety in the presence of a target cell, such as a cancer cell or bacterial cell, or a target virus and evaluating the binding of the cell comprising the CAR or TCR to the binding agent and/or evaluating the binding of the cell comprising the CAR or TCR to the target cell or target virus. Accordingly, methods of making a complex and the complex itself comprising a cell, such as a T cell, which comprises a CAR or TCR specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), joined to a binding agent, such as a hapten, ligand, or antibody or antibody fragment thereof comprising said target moiety, through a CAR or TCR mediated binding to said target moiety, wherein said binding agent is further bound to or interacts with a target cell, such as a cancer cell or bacterial cell, or a target virus are contemplated. In some alternatives, the antibody or binding fragment thereof, which is conjugated to the target moiety, is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a binding fragment thereof. In some alternatives, the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/C1/C6 R1= NH2- R2= -C1 R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -C1 R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;,Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3′,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2′,4,4′,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-
Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB 1089(Seocalcitol),EB 1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -Cl R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -Cl R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HClo1, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine inposition 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HCl01 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2′,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-(3-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = C1 R3 = CN R4 = C1 R5 = C1 R6 = Cl), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = CN R4 = C1 R5 = C1 R6 = Cl), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = C1 R3 = CN R4 = OH R5 = C1 R6 = Cl), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = Cl R3 = COOH R4 = H R5 = Cl R6 = Cl), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = Cl R2 = Cl R3 = Cl R4 = Cl R5 = Cl R6 = Cl), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = Cl R3 = H R4 = Cl R5 = Cl R6 = Cl ), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,, HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners - 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = Cl R2 = Cl R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = Cl R2 = Cl R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = Cl R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-
nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies (C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies (MAb: AM7B2.1), Anti Atrazine Antibodies(ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3′,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Tryl96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens. -
FIGS. 1A and 1B shows the initial phospholipid ether (PLE) CAR T cell tumor targeting or cancer cell targeting (CTCT) agents. As shown in panels A and B are the structure of FL-PLE (1A) and ProFL-PLE (1B). (i) FL (fluorescein), the target for CAR T cells. (ii) Polyetheneglycol (PEG), the spacer used to extend the target an ideal distance from the cell surface. (iii & iv) PLE, iii is the polar head group and iv is the hydrophobic tail for incorporation or tethering into the cell plasma membrane. (v) Masking moiety, to prevent anti-FLCAR T cell recognition. (vi) The cleavage point where ProFL-PLE is unmasked. Unmasking to occur once or just before anti-FLCAR T-cells are in the reactive oxygen species (ROS) rich environment afforded by the tumor. This will in turn create the FL-PLE. -
FIG. 2 shows the schematic of FL-PLE and ProFL-PLE. As shown in the letters on the Figure, (a) shows that a PLE is embedded into a lipid raft on the cell membrane of a tumor cell. As shown in (b) is a FL-PLE with a single PEG spacer compared to a four PEG spacer that is shown in (c). The PEG spacer will be varied until the optimal spacer length to antiFL CAR T-cell pair is identified. As shown in (d), is a ProFL-PLE containing a steric hindrance “masking” moiety and an “optimal” PEG spacer. As shown in (e), is the conversion of ProFL-PLE to FL-PLE due to masking moiety cleavage once inside the ROS rich tumor microenvironment. The FL-PLE is now bioavailable to antiFL CAR T-cells. -
FIG. 3 shows the synthesis routes for FL-PLE. -
FIG. 4 shows the resulting NMR data in a 1D NMR spectra of the synthesized FL-PLE, which was subjected to NMR analysis. The 1D-spectra from the NMR identified the synthesized product as FL-PLE that was shown in the synthesis ofFIG. 3 . -
FIG. 5 shows Synthesis Routes for ProFL-PLE. -
FIG. 6 shows the NMR of ProFL-PLE. The Synthesized ProFL-PLE was subjected to NMR analysis. Spectra from the NMR identify the synthesized product as ProFL-PLE that was shown in the synthesis ofFIG. 5 . -
FIGS. 7A-7E shows tumor targeting & integration of FL-PLE. (7A-7D) Cells were incubated with 5 µM FL-PLE overnight then cells were analyzed by flow or confocal microscope. The cells may also be incubated with 1 nM, 5 nM, 10 nM, 100 nM, 200 nM, 300 nM 400 nM, 500 nM, 600 nM, 700 nM, 800 nM, 1 µM, 5 µM, 10 µM, 15 µM, 20 µM or 25 µM FL-PLE overnight. The level of FL-PLE integration into the cell membrane was identified by the signal intensity emitted from the fluorescein moiety of the FL-PLE. (7A) Shows FL-PLE is able to integrate into multiple cancers: Be2 (neuroblastoma), U87 (glioblastoma), and daoy (medulloblastoma). (7B) U87 cells were incubated overnight in the presence of 0, 0.1, 1, or 5 µM FL-PLE and then subjected to flow analysis. These results demonstrate that FL-PLE integration into the cancer cell membrane is concentration dependent. (7C) U87 cells were incubated overnight in the presence of 5 µM FL-PLE, washed to remove residual FL-PLE, cultured in fresh (FL-PLE free) media for up to 4 days, and then subjected to flow analysis. Results demonstrate a multiday FL-PLE retention time. As shown, the blue and green stain is actually throughout the cells. Alternatively, the cells may be incubated with 1 nM, 5 nM, 10 nM, 100 nM, 200 nM, 300 nM 400 nM, 500 nM, 600 nM, 700 nM, 800 nM, 1 µM, 5 µM, 10 µM, 15 µM, 20 µM or 25 µM FL-PLE (7D) Confocal images show that FL-PLE integrates over the whole cell surface (U87 cells). The FL-PLE is shown in green and the nucleus is stained with DAPI which is shown in blue. (7E) After a glioblastoma (U87 cells) tumor was established in a group of mice by intracranial injection, the mice received an intravenous injection of FL-PLE. Mice were sacrificed and brains were harvested at various time points post FL-PLE injection. The fluorescent image of a brain harvested 2 days post FL-PLE injection demonstrates that FL-PLE preferentially targets and integrates into the tumor in an in vivo environment. As shown, the FL-PLE is in a targeted area as demonstrated by the circular area within the right quadrant of the brain shown inFIG. 7E . -
FIG. 8 shows that the FL moiety is accessible for binding. U87 cells were incubated with 5 µM FL-PLE overnight then imaged by confocal microscopy. Same asFIG. 7D except this time U87 cells (nucleus shown in blue, DAPI) with FL-PLE (green) integrated into the membrane were stained with an antifluorescein antibody conjugated with an Alex 647 fluorophore (grey). These images demonstrate that the FL moiety is accessible for binding. As shown inFIG. 8 , the anti-FL antibody is bound to the FL-PLE. -
FIGS. 9A-9C shows the results of CAR T cell recognition and activation through FL-PLE (in vitro). K562 (leukemia) cells were incubated with FL-PLE overnight. Cell integration of FL-PLE was analyzed by flow cytometry (9A). There is a clear shift from the control K562 parental with the K562 parental incubated with 5 mM FL-PLE whereas there is a very slight shift with K562 parental incubated with 0.5 mM FL-PLE. This slight shift corresponds to a difference in the amount of FL exposed on the surface of the cell for CAR T cell recognition. Also the K562+OKT3 cells (a cell line created to test the endogenous activation of T cells through the TCR) match the K562 parental exactly, as expected. These cells were used in a chromium release assay (9B) and a cytokine release assay (9C) to test the activation of CD8+ antiFL CAR T cells compared with a CD8+ mock T cells. From these experiments antiFL CAR T cells can recognize the FL moiety of the FL-PLE integrated into the plasma membrane and able to activate. The amount of the activation is dependent on the amount of FL exposed on the surface of the cell. As shown in 9B, in the K562 parental cells panel, the specific lysis was the same for the CD8+ mock cells and the CD8+ AntiFL CAR bearing cells. In the K562 + OKT3 panel ofFIG. 9B , the specific lysis was the same for the CD8+ mock cells and the CD8+ AntiFL CAR bearing cells. In the bottom panels ofFIG. 9B , the CD8+ AntiFL CAR cells showed a higher percentage of specific lysis. InFIG. 9C , the CD8+ antiFL CAR cells exhibited better Il-2, TNFα and IFN γ release than the CD8+ mock cells. -
FIG. 10 shows the results of CAR T cell recognition and activation through FL-PLE (in vivo). Winn Assay: U87 cells harboring a green fluorescent protein and firefly luciferase fusion protein (GFP-ffLuc) were incubated with FL-PLE overnight. Note, the GFP-ffLuc allows for real-time monitoring of tumor progression via luminescent imaging. These cells were then mixed with CD8+ antiFL CAR T cells or CD8+ mock T cells at a 1:1 or 10:1 effector to target (E:T) ratio. Cell mixtures were injected into the brain of a mouse and tumor engraftment was monitored by luminescent flux over time. Here the antiFL CAR T cell is able to activate and slow down the engraftment of the tumor at a 10:1 (E:T). This demonstrates that the FL-PLE works as a target for CAR T-cell recognition in a living model. -
FIG. 11 shows ProFL-PLE integration into cells and unmasking. U87 cells were incubated with 5 µM ProFL-PLE overnight then imaged by confocal microscopy. The nucleus of the cells were stained with DAPI (blue). Same procedure asFIG. 5D . ProFL-PLE is not fluorescent due to the presence of the masking agent, a phenolic hydroxy group. When ProFL-PLE is introduced to a ROS environment, as modeled by the presence of H2O2, it is unmasked revealing the FL moiety. Therefore the unmasked ProFL-PLE has the capability to emit green fluorescence (green). Below is an image of ProFL-PLE integrated into the U87 cells with almost no green fluorescence. Cells that were exposed to ROS now emit green fluorescence, showing that ProFL-PLE can be unmasked and is integrated into the cell membrane. -
FIG. 12 shows an example of a construction scheme for the synthesis of fluorescein-PEG-phosphatidylcholine. -
FIG. 13 shows an example of a construction scheme for the synthesis of fluorescein-PEG. -
FIG. 14 shows the construction scheme for ProFL-NHS. -
FIG. 15 shows a commercially available ROS detection system. As shown, a development of novel fluorescence probes can reliably detect reactive oxygen species and distinguish specific species. (Journal of Biological Chemistry 2003 278(5) 3170-3175, incorporated by reference in its entirety herein). - In the description that follows, the terms should be given their plain and ordinary meaning when read in light of the specification. One of skill in the art would understand the terms as used in view of the whole specification.
- As used herein, “a” or “an” may mean one or more than one.
- As used herein, the term “about” indicates that a value includes the inherent variation of error for the method being employed to determine a value, or the variation that exists among experiments.
- “Chimeric antigen receptor” or “CAR” or “Chimeric T cell receptor have their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a synthetically designed receptor comprising a ligand binding domain of an antibody or other protein sequence that binds to a molecule associated with the disease or disorder and is linked via a spacer domain to one or more intracellular signaling domains of a T cell or other receptors, such as a costimulatory domain. Chimeric receptor can also be referred to as artificial T cell receptors, chimeric T cell receptors, chimeric immunoreceptors, and chimeric antigen receptors (CARs). These CARs are engineered receptors that can graft an arbitrary specificity onto an immune receptor cell. The term chimeric antigen receptors or “CARs” are also considered by some investigators to include the antibody or antibody fragment, the spacer, signaling domain, and transmembrane region. However, due to the surprising effects of modifying the different components or domains of the CAR described herein, such as the epitope binding region (for example, antibody fragment, scFv, or portion thereof), spacer, transmembrane domain, and/ or signaling domain), the components of the CAR are frequently distinguished throughout this disclosure in terms of independent elements. In some alternatives, the spacer for the chimeric antigen receptor is selected (e.g., for a particular length of amino acids in the spacer) to achieve desired binding characteristics for the CAR. CARs having varying lengths of spacers, e.g., presented on cells are then screened for the ability to bind or interact with a target moiety to which the CAR is directed. Exemplary target moieties include a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)). The target moieties to which the CARs bind or interact can be presented on a substrate, such as a membrane, bead, or support (e.g., a well) or a binding agent, such as a lipid (e.g., PLE), hapten, ligand, or antibody, or binding fragment thereof, preferably a binding agent that has specificity for an antigen present on a cancer cell or pathogen such as, a virus or bacteria. By one approach, the substrate or binding agent comprising the desired target moiety is contacted with a plurality of cells comprising a CAR or TCR specific for said target moiety and the level or amount of binding of the cells comprising the CAR or TCR to the target moiety present on the substrate or binding agent is determined. Such an evaluation of binding may include staining for cells bound to target moieties or evaluation of fluorescence or loss of fluorescence. Again, modifications to the CAR structure, such as varying spacer lengths, can be evaluated in this manner. In some approaches, a target cell is also provided such that the method comprises contacting a cell, such as a T cell, which comprises a CAR or TCR that is specific for a target moiety, such as a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)), with a binding agent such as a hapten, ligand, or antibody or antibody fragment thereof joined to said target moiety in the presence of a target cell, such as a cancer cell or bacterial cell, or a target virus and evaluating the binding of the cell comprising the CAR or TCR to the binding agent and/or evaluating the binding of the cell comprising the CAR or TCR to the target cell or target virus. The variation of the different elements of the CAR can, for example, lead to stronger binding affinity for a specific epitope or antigen. In some alternatives, the antibody or binding fragment thereof, which is conjugated to the target moiety, used in these evaluations comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, tefibazumab, actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- “Co-stimulatory domain,” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a signaling moiety that provides to T cells a signal which, in addition to the primary signal provided by for instance the CD3 zeta chain of the TCR/CD3 complex, mediates a T cell response, including, but not limited to, activation, proliferation, differentiation, cytokine secretion, and the like. A co-stimulatory domain can include all or a portion of, but is not limited to, CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83. In some alternatives, the co-stimulatory domain is an intracellular signaling domain that interacts with other intracellular mediators to mediate a cell response including activation, proliferation, differentiation and cytokine secretion, and the like. In some alternatives, herein the co-stimulatory domain comprises 41bb and CD3zeta. In some alternatives, a T cell is provided, wherein the T cell comprises a CAR specific for the targeting moiety on the composition. In some alternatives, the T cell further comprise an 806 CAR (anti-EGFR(806)(41BB-CD3zeta CAR).
- In some alternatives described herein, the CAR is specific for a lipid or peptide that targets a tumor or cancer cell, wherein the lipid or peptide comprises a target moiety and the CAR can specifically bind to said lipid through an interaction with said target moiety. In some alternatives, the lipid is a phospholipid ether. In some alternatives described herein, the CAR is specific for a phospholipid ether, wherein the phospholipid ether comprises a target moiety and the CAR specifically binds to said phospholipid ether through an interaction with said target moiety. In some alternatives herein, the CAR comprises a co-stimulatory domain. In some alternatives the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof.
- In some alternatives, the CAR is specific for a target moiety affixed to an antibody or binding fragment thereof, wherein the CAR specifically binds to said antibody or binding fragment thereof through an interaction with said target moiety. Exemplary target moieties, which can be conjugated to said antibody or binding fragment thereof include a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)). In some alternatives, the antibody or binding fragment thereof is specific for an antigen or ligand present on a cancer cell or a pathogen (e.g., viral or bacterial pathogen). In some alternatives, the antibody or binding fragment thereof is specific for an antigen or ligand present on a tumor cell, a virus, preferably a chronic virus (e.g., a hepatitis virus, such as HBV or HCV, or HIV), or a bacterial cell. In some alternatives herein, the CAR comprises a co-stimulatory domain. In some alternatives the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof. In some alternatives, the antibody or binding fragment thereof, which is joined to said target moiety, comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, tefibazumab, actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- In some alternatives, the chimeric receptor nucleic acid comprises a polynucleotide coding for a transmembrane domain. The transmembrane domain provides for anchoring of the chimeric receptor in the membrane.
- In some alternatives, a complex is provided, wherein the complex comprises a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to a lipid wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety.
- In some alternatives, a complex is provided, wherein the complex comprises a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to an antibody or binding fragment thereof, wherein the antibody or binding fragment thereof comprises a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety. In some alternatives, the antibody or binding fragment thereof is further joined to an antigen or ligand present on a cancer cell or a pathogen (e.g., viral or bacterial pathogen). In some alternatives, the antibody or binding fragment thereof is joined to an antigen or ligand present on a tumor cell, a virus, preferably a chronic virus (e.g., a hepatitis virus, such as HBV or HCV, or HIV), or a bacterial cell. In some alternatives, the CAR comprises a co-stimulatory domain. In some alternatives the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof. In some alternatives, the target moiety is present on an antibody or binding fragment thereof, which are specific for an antigen on a cancer cell or pathogen (e.g., a virus or bacterial cell), and said target moiety is bound by a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- A “T cell receptor” or “TCR” has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a molecule that is found on the surface of T lymphocytes or T cells that is responsible for the recognition of fragments of antigen bound to a major histocompatibility complex molecule.
- “Target moiety” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a specific group or site on a molecule or chemical that is a binding target for another chemical or protein of interest. In some alternatives described herein, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)). In some alternatives, a complex is provided, wherein the complex comprises a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to a lipid wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In further alternatives, a complex is provided, wherein the complex comprises a chimeric antigen receptor (CAR) or a T cell receptor (TCR) joined to an antibody or binding fragment thereof, wherein the antibody or binding fragment thereof comprises a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety. In some alternatives, the antibody or binding fragment thereof is further joined to an antigen or ligand present on a cancer cell or a pathogen (e.g., viral or bacterial pathogen). In some alternatives, the antibody or binding fragment thereof is joined to an antigen or ligand present on a tumor cell, a virus, preferably a chronic virus (e.g., a hepatitis virus, such as HBV or HCV, or HIV), or a bacterial cell. In some alternatives, the CAR comprises a co-stimulatory domain. In some alternatives the co-stimulatory domain is CD27, CD28, 4-1BB, OX40, CD30, CD40, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, or a ligand that specifically binds with CD83, or a portion thereof. In some alternatives, the target moiety is present on an antibody or binding fragment thereof, which are specific for an antigen on a cancer cell or pathogen (e.g., a virus or bacterial cell), and said target moiety is bound by a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- “Biotin” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a water-soluble B-vitamin. In the alternatives herein, biotin is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor. In some alternatives, the lipid is a phospholipid ether.
- “Digoxigenin” or “DIG” as described herein, has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a steroid found exclusively in the flowers and leaves of plants. In the alternatives herein, DIG is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor. In some alternatives, the lipid is a phospholipid ether.
- “2,4-Dinitrophenol,” “2,4-DNP,” “Dinitrophenol” or “DNP” has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an organic compound with the formula HOC6H3(NO2)2. In the alternatives herein, DNP is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor. In some alternatives, the lipid is a phospholipid ether.
- “Fluorescein” and fluorescein derivitives has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a synthetic organic compound that is soluble in water and alcohol. It is widely used as a fluorescent tracer for many applications. In some alternatives herein, fluorescein is a target moiety on a lipid that is recognized and bound by a chimeric antigen receptor. In some alternatives, the lipid is a phospholipid ether. In some alternatives, fluorescein is a target moiety on an antibody or binding fragment thereof, which are specific for an antigen on a cancer cell or pathogen (e.g., a virus or bacterial cell), and said target moiety is bound by a chimeric antigen receptor present on the surface of a cell (e.g., a T cell) such that the cell having the chimeric antigen receptor is redirected to the cancer cell or pathogen.
- “Lipid” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a class of organic compounds that comprise carbon chains, fatty acids or a fatty acid derivative that is typically insoluble in water but can integrate into or mix with hydrophobic or organic solvents. Without being limiting, lipids can include fats, waxes, fat soluble vitamins, monoglycerides, diglycerides, triglycerides, sphingolipids, cerebrosides, ceramides, and phospholipids. As described herein are amphiphilic lipids that can have a polar head group and a hydrophobic moiety or hydrophobic group. “Hydrophobic group” or hydrophobic moiety has their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a molecule or a part of a molecule that is repelled from a mass of water and tends to be non-polar. This can include alkanes, oils and fats. Without being limiting, lipids can be glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids and polyketides. In the alternatives, herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid comprises a polar head group and a hydrophobic moiety. In some alternatives, the hydrophobic moiety is a hydrophobic carbon tail. In some alternatives the hydrophobic carbon tail is saturated or unsaturated. In some alternatives, the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value. In some alternatives, the hydrophobic moiety is a steroid or a cholesterol. In some alternatives, the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid contains branched alkyl tails.
- In some alternatives, the lipid can be a sphingolipid. The sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. In some alternatives, the lipid is a glycosphingolipid.
- As provided herein, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group comprises a fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol.
- In some alternatives, the lipid is a single chain alkylphospholipid.
- In some alternatives, the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine. In some alternatives, the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine. Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety). In some alternatives of the lipids described herein, a choline within the polar head group can be substituted with a piperidine moiety. In some alternatives, the lipid is an anticancer alkylphospholipid. Anticancer phospholipids are described by vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).
- In some alternatives, the lipids provided herein are synthetic and structurally related antitumor agents that interact with a cell membrane. These types of synthetic lipids are alkylphospholipids and are described by e.g., van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein). Without being limiting, the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and Erufosine. In some alternatives, the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine. In some alternatives, the lipid is a stable analog of lysophosphatidylcholine. In some alternatives, the lipid is a thio-ether variant of edelfosine, or 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine. In some alternatives, the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine.
- “Polar-head group” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, the hydrophilic group of a lipid, such as a phospholipid. “Phospholipids” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a specific class of lipids that can form lipid bilayers due to their amphiphilic characteristic. The phospholipid molecule comprises at least one hydrophobic fatty acid “tail” and a hydrophilic “head” or “polar-head group.” In the alternative herein, the phospholipid or phospholipid ether comprises a polar-head group. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar-head group (e.g., comprising an aromatic ring) and a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid comprises a polar head group. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the phospholipid ether comprises a target moiety and the CAR is joined to said phospholipid ether through an interaction with said target moiety. In some alternatives, the phospholipid ether comprises a polar-head group and a carbon alkyl chain. In some alternatives the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the sugar is a glycerol. In some alternatives, the polar head group comprises a sugar group. In some alternatives, the lipid comprises a mannose-containing head group. In some alternatives, the polar head group comprises sphingosine. In some alternatives, the polar head group comprises a glucose. In some alternatives, the polar head group comprises a di-, tri- or tetra-saccharide. In some alternatives, the lipid is a glucosylcerebroside. In some alternatives, the lipid is a lactosylceramide. In some alternatives, the lipid is a glycolipid. In some alternatives, the glycolipid comprises sugar units such as n-glucose, n-galactose or N-actyl-n-galactosamine. In some alternatives, the lipid comprises a hydrocarbon ring such as a sterol.
- In some alternatives, the polar head group of the lipid comprises glycerol. In some alternatives, the polar head group of the lipid comprises a phosphate group. In some alternatives, the polar head group of the lipid comprises choline. In some alternatives, the lipid is a phosphatidylethanolomine. In some alternatives, the lipid is a phosphatidylinositol. In some alternatives, the lipid comprises a sphingoid base backbone. In some alternatives, the lipid comprises a sterol lipid, such as cholesterol or its derivatives. In some alternatives, the lipid comprises saccharolipids. In some alternatives, the polar head group comprises choline, phosphate and/or glycerol.
- In some alternatives, the lipid is a glycolipid. In some alternatives, the lipid comprises a sugar. In some alternatives, the lipid is derived from sphingosine. In some alternatives, the lipid is a glycerol-glycolipid or a sphingo-glycolipid.
- In some alternatives, the lipid is an ether lipid with branched hydrophobic chains.
- “Saturated” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a fatty acid molecule, in which there are no double bonds within the carbon molecules. Unsaturated as described herein indicates that there are one or more double bonds in a fatty acid chain. In some alternatives herein a complex comprising a lipid is provided. In some alternatives, the lipid comprises a fatty acid chain, in which the fatty acid is saturated or unsaturated.
- “Alkyl” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an alkyl substituent that has a missing hydrogen.
- An “alkenyl” group has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an unsaturated hydrocarbon that contains at least one carbon-carbon double bond.
- An “alkynyl” group has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, an unsaturated hydrocarbon containing at least one carbon-carbon triple bond.
- “Terpenoid” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a molecule that is derived from five carbon isoprene units. Steroids and sterols can be produced from terpenoid precursors. For example steroids and cholesterol can be biosynthesized by terpenoid precursors.
- “Phospholipid ether” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a lipid in which one or more of the carbon atoms on a polar head group are bonded to an alkyl chain via an ether linkage as opposed to the more common ester linkage. In some alternatives, the polar head group is a glycerol.
- “Antibody” has its plain and ordinary meaning when read in light of the specification. The term antibody refers to an antibody and in some circumstances refers to a binding fragment of an antibody. A labeled antibody includes an antibody or binding fragment thereof, in some circumstances, joined to a detectable moiety (for example, a target moiety such as, a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC))). The labeled antibody or binding fragment thereof described herein includes an antibody or binding fragment thereof that specifically binds an antigen of a cancer cell or an antigen of a pathogen. In some alternatives, the antibody or binding fragment thereof, which can be joined to a target moiety or provided as an additional therapy in any one or more of the therapies described herein comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, tefibazumab, actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- Non-limiting examples of an antibody or binding fragment thereof, which can be conjugated with target moieties, include monoclonal antibodies, bispecific antibodies, Fab, Fab2, Fab3, scFv, Bis-scFv, minibody, triabody, diabody, tetrabody, VhH domain, V-NAR domain, IgNAR, and camel Ig. Additional examples of an antibody are IgG (e.g., IgG1, IgG2, IgG3, or IgG4), IgM, IgE, IgD, and IgA. Non-limiting examples of antibodies include human antibodies, humanized antibodies, or chimeric antibodies. Non-limiting examples of recombinant antibodies include antibodies that specifically bind to NGF.
- An antibody or binding fragment thereof that specifically binds an antigen of a cancer cell, which can be conjugated with target moieties, may include, for example, abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, or zatuximab, or a derivative, analogue, or binding fragment thereof. Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the cancer cells having the antigen specific for the antibodies or binding fragments thereof.
- Any of the cancer specific antibodies described herein may bind an antigen on a cancer cell, for example on a tumor cell. Specific tumor cell antigens to which antibodies can be generated, which can be conjugated with target moieties, may include, for example, angiopoietins, transmembrane receptors, cell adhesion molecules, cluster of differentiation molecules, gangliosides, glycoproteins, growth factors, integrins, interleukins, Notch receptors, syn-notch receptors, syn-notch, transmembrane glycoproteins, tumor necrosis factors, or tyrosine kinases. In some embodiments, a tumor cell antigen may include, for example, 5T4, B7-H3, carbonic anhydrase IX, carcinoembryonic antigen, CA-125, CD-3, CD-19, CD-20, CD-22, CD-30, CD-33, CD-38, CD-40, CD-51, CD-52, CD-56, CD-70, CD-74, CD-79b, CD-138, CD-221, CD-319, CD-326,
cell adhesion molecule 5, CTLA-4, cytokeratin polypeptides,death receptor 2, DLL4, EGFL7, EGFR, endosialin, EpCAM, FAP, FR-alpha, fibronectin, frizzled receptors, GD2, GPNMB, HER-1, HER-2, HER-3, IGF-IR, IGLF2, LOXL2, mesothelin, MS4A1, mucin 5AC, MUC1, Nectin-4, neuropilin, N-glycolyl GM3, PSMA, SLAMF7, TAG-72, TRAIL, TYRP1, VEGF, or other cancer expressing antigens. Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the cancer cells having the antigen specific for the antibodies or binding fragments thereof. Administration may be by intravenous administration. - An antibody or binding fragment thereof that specifically binds a pathogen, which can be conjugated with target moieties, may include an antibody or binding fragment thereof that binds a viral antigen on a virus or that binds a bacterial antigen on a bacterial cell. Antibodies that bind a viral antigen may include, for example, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, or umavizumab or a derivative, analogue, or binding fragment thereof. Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the virus having the antigen specific for the antibodies or binding fragments thereof. Administration may be by intravenous administration.
- Antibodies that bind a bacterial antigen, which can be conjugated with target moieties, may include, for example, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a derivative, analogue, or binding fragment thereof. Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the bacterial cells having the antigen specific for the antibodies or binding fragments thereof. Administration may be by intravenous administration.
- Additional pathogenic antibodies, which can be conjugated with target moieties, may include actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof. Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the pathogen having the antigen specific for the antibodies or binding fragments thereof. Administration may be by intravenous administration.
- Any of the pathogenic specific antibodies or binding fragments thereof, which can be conjugated with target moieties, may bind specifically to a viral antigen or a bacterial antigen, including, for example by binding to an antigen of a Bacillus, a Candida, a Clostridium, a cytomegalovirus, an Ebola virus, an Escherichia, a Gram-negative bacteria, a Gram-positive bacteria, a hepatitis virus, a herpes virus, an HIV, an influenza virus, a Pseudomonas, a Staphylococcus, or a syncytial virus. Such antibodies or binding fragments thereof can be joined to a target moiety (e.g., a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, digoxigenin, dinitrophenol, green fluorescent protein (GFP), yellow fluorescent protein, orange fluorescent protein, red fluorescent protein, far red fluorescent protein, or fluorescein (e.g., Fluorescein isothiocyanate (FITC)) and such conjugated antibodies can be administered to patients in conjunction with (e.g., before, after or simultaneous with) cells (e.g., T cells) having chimeric antigen receptors specific for said target moiety such that the cells having the chimeric antigen receptors are redirected to the pathogen having the antigen specific for the antibodies or binding fragments thereof. Administration may be by intravenous administration.
- Any of the antibodies or binding fragments herein provided herein may be linked to a target moiety as described herein. The target moiety may include, for example, a a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin,, a digoxigenin, a dinotrophenol or a fluorescein. In some embodiments, the target moiety is fluorescein isothiocyanate (FITC). Accordingly, the CAR described herein may bind to the target moiety on the antibody, thereby binding the cancer cell or pathogenic cell through the labeled antibody or fragment thereof.
- Several types of “spacers” are contemplated for use with embodiments described herein. The spacer for a chimeric antigen receptor refers to a polypeptide spacer, wherein the length of the spacer is selected to increase or improve the ability of the chimeric antigen receptor to bind its target. The lipid can also comprise a spacer that separates the target moiety from the lipid and is bound to the polar-head group of the lipid. Selected polypeptide spacers for use with chimeric antigen receptors may be screened so as to identify a specific spacer, which promotes a desired binding characteristic to a target moiety (e.g., a desired receptor interaction or a desired avidity with the receptor). Regarding the spacers that are specific for a lipid, the spacer of the lipid can comprise a poly(carboxybetaine), peptide, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, PEG spacer, a Hapten spacer, a small peptide or an alkane chain. In some alternatives, the hapten spacer comprises two haptens and is referred to as a hapten (2X) spacer. In some alternatives, the hapten spacer comprises three haptens and is referred to as a hapten (3X) spacer. In some alternatives, the hapten spacer comprises four haptens and is referred to as a hapten (4X) spacer. In some alternatives, the hapten spacer comprises five haptens and is referred to as a hapten (5X) spacer. In some alternatives, the hapten spacer comprises two, three, four or five different haptens. In some alternatives, the lipid comprises a hydrophobic group, such as an alkane chain. In some alternatives, the alkane chain can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons, or any number of carbons in between a range defined by any two aforementioned values. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values.
- “Hapten” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a small molecule binding moiety, which can be substituted for an scFvT or antibody. The three key advantages are that it is designed to (i) not trigger an immune response or a significantly diminished immune response, (ii) bind targets which may or may not be proteins or peptides or may be difficult to create a antibody/scFv binding moiety; and (iii) that it can be better optimized for binding/affinity. In some alternatives, the hapten used comprises Alexa Fluor 405, Cascade Blue, Alexa Fluor 488, BODIPY, Dansyl chloride, Oregon Green, Lucifer yellow, Rhodamine, Tetramethylrhodamine, Nitrotyrosine, digoxigenin, 2,4-Dichlorophenoxyacetic acid, Atrazine (2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine), Nicotine (3-(1-Methyl-2-pyrrolidyl)pyridine, Black Leaf), Morphine (morph, Morphine Sulfate), 2,4-DINITROCHLOROBENZENE (1-Chloro-2,4-dinitrobenzene; DNCB;Dinitrochlorobenzene), 4-chloro-6-(ethylamino)-1,3,5-triazine-2-(6-aminohexanecarboxylic acid), Structurally related s-triazines (Modifications: H/Cl/C6 R1= NH2- R2= -Cl R3= -NH-(CH2)5-COOH; iPr/Cl/nBu R1= (CH3)2-CH-NH- R2= -C1 R3= -NH-(CH2)3-(CH3)), Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine), Deethylatrazine (DEA) (Structurally related s- triazines), Deisopropylatrazine (DIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), Deethyldeisopropylatrazine (DEDIA) (Structurally related s- triazines), HydroxyAtrazine(HA) (Structurally related s- triazines), DeisopropylHydroxyAtrazine(DIHA) (Structurally related s- triazines), DeethylDeisopropylHydroxyAtrazine(DEDIHA) (Structurally related s- triazines), Simazine (Structurally related s- triazines), Desmetryne (Structurally related s- triazines), Prometryne (Structurally related s- triazines), 2-hydroxyatrazine (atrazine derivative), 2-hydroxypropazine (structurally related s-triazine), 2-hydroxysimazine, N-(4-Amine-6-hydroxy-[1,3,5]triazin-2-yl)-4-aminobutanoic Acid (Modification: R1= NH2 R2= NH(CH2)3COOH R3= OH), SulcoFuron, 5-chloro-2-{4-chloro-2-[3-(3,4-dichlorophenyl)ureido]phenoxy}benzenesulfonic acid, FlucoFuron (1,3-bis(4-chloro-α,α,α-trifluoro-m-tolyl)urea), Agatharesinol, Sequirin C, Sugiresinol, Hydroxysugiresinol, Hinokiresinol, Coniferyl alcohol, Cinnamyl alcohol, p-Coumaric acid, Cinnamic acid, p-Coumaric acid, Cinnamic acid, Hinokinin, Guaiacylglycerol- beta-guaiacyl ether, Morphine-3-glucuronide(M3G), Codeine, Nor-Codeine, 6-Monoacetylmorphine, (+) Methamphetamine, Ceftazidime, Phenobarbital, p-hydroxyPhenobarbital, p-aminophenobarbital, Cyclobarbital, 3′-Ketocyclobarbital, 3′-Hydroxycyclobarbital, Secobarbital, Barbital, Metharbital, Barbituric acid, Thiopental, Thiobarbituric acid, Primidone, Glutethimide, Pentobarbital, Heroin, Diacetylmorphine, Levallorphan, L-11-Allyl-1,2,3,9,10,10a-hexahydro-4H-10,4a-iminoethanophenanthren-6-ol, Pethidine (Demerol; Dolantin; Meperidine; Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate; Isonipecaine), Methamphetamine, d-Desoxyephedrine; Methedrine; Tolpropamine; Pratalgin; Pragman. Benzoylecgonine, 3-Carboxymethylmorphine, Cocaine, 5-benzimidazolecarboxylic acid, ABA (4-acetyl benzoic acid), Dexamethasone, Flumethasone, 6alpha, 9 alpha-difluoro-11 beta,17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 9 alpha-fluoro-11 beta,17,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione, 9-alpha-fluroprednisolone, Desoxymethasone, Triamcinolone, 9 alpha-fluoro-11 beta,16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, Fluocortolone, 6 alpha-fluoro-11 beta,21-dihydroxypregna-1,4-diene-3,20-dione, Cortisol, 11 beta,17,21-trihydroxypregna-4-ene-3,20-dione, Prednisone, 17,21-dihydroxypregn-4-ene-3,11,20-trione, Methylprednisolone, 11 beta,17,21-trihydroxy-6 alpha-methylpregna-1,4-diene-3,20-dione, Triamcinolone hexacetonide, 21-(3,3-dimethyl-1-oxobutoxy)-9 alpha-fluoro-11-hydroxy-16,17-[(1-methylethylidene) bis(oxy)]pregna-1,4-diene-3,20-dione, Carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate, BFNP (3-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]amino]propanoic acid), Carbofuran derivative, 2,3-dihydro-2,2-dimethyl-7-benzofuranol, Bendiocarb, Carbaryl, Methiocarb, Propoxur, Aldicarb, Methomyl, Benalaxyl, methyl N-(phenylacetyl)-N-(2,6-xylyl)-DL-alaninate, Bn-Ba (4-[2-(N-phenylacetyl-N-2,6-xylylamino)propionamido] butyric acid), Bn-COOH (4-[2-(N-phenylacetyl-N-2,6-xylyl-DL-alanine), Benalaxyl derivative, Furalaxyl, Metalaxyl, Acetochlor, Dimetachlor, Metolachlor, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Benzoylprop-ethyl, 2,4,5-Trichlorophenoxyacetic acid, 2-chloro-6′-ethyl-N-(2-methoxy-1-methylethyl)acet-o-toluidine, Diethathyl-ethyl, Benzoylprop-ethyl, Propachlor, Propachlor, 2,4,5-Trichlorophenoxyacetic acid, 2,4,5,T ; Weedone, 2,4-Dichlorophenoxybutyric acid (2,4-DB), 2,4-DB; Butanoic acid, 4-(2,4-dichlorophenoxy)- ; Butoxone; Embutone, MCPA, 2-Methyl-4-chlorophenoxyacetic acid; Metaxon, Dichlorprop (2,4-DP), 1-[(2-chloro)phenylsulfonyl]monoamidosuccinic acid, Chlorsulfuron, chlorbromuron, amidosulfuron, chlortoluron, isoproturon, diuron, Linuron O-Methyl-O-(4-nitrophenyl)-N-(4-carboxybutyl)-phosphoramidothioate Parathion-methyl, O,O-dimethyl O-4-nitrophenyl phosphorothioate; Methaphos; Wolfatox; Dimethylparathion; Metacide.,Parathion-ethyl, DIETHYL P-NITROPHENYL THIOPHOSPHATE; O,O-DIETHYL O-(P-NITROPHENYL) PHOSPHOROTHIOATE;,Fenitrothion, O,O-dimetyl O-4-nitro-m-tolyl phosphorothioate, Fenthion,O,O-dimethyl O-4-methylthio-m-tolyl phosphorothioate, Bromophos,O-4-bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate, chlorpyrifos-methyl,O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate,Oxidized parathion-methyl,Paraoxon, phosphoric acid, O,O-diethyl O-(4-nitrophenyl) ester,Diazinon,O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate,Azinphos-methyl, pirimiphos-methyl, O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate, Methidathion, S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate, Dimethylchlorothiophosphate, 4-NITROPHENOL, p-nitrophenol, Phenolic derivative (Modification On benzene ring ; R1=OH R2=NO2 R3=H R4=CH2COOH R5=H R6=H); 2-Nitrophenol, o-Nitrophenol, 3-Nitrophenol, m-nitrophenol, 2,4-Dinitrophenol, 3,4-Dinitrophenol, 2,5-Dinitrophenol, 2,4-Dinitro-6-methylphenol, 2,3,6-trinitrophenol, 2-Chlorophenol, 4-Chloro-3-methylphenol,Fenitroxon, 3-Methyl-4-nitrophenol, Nonylphenol,HOM(3-[2-hydroxy-5nitro benzylthio ] propionic acid, Phenol,Delor 103, Polychlorinated Biphenyls, Delor 104, Polychlorinated Biphenyls, Delor 105,Polychlorinated Biphenyls,Delor 106, 4,4′-Dichlorobiphenyl,PCB congeners, 2,4,4′-Trichlorobiphenyl, PCB congeners,2,4′-Bichlorobiphenyl, PCB congeners, 2,2′-Dichlorobiphenyl,PCB congeners, 2,4,5-Trichlorobiphenyl,PCB congeners, 3,3′,4,4′-Tetrachlorobiphenyl,PCB congeners, PCB congeners, 2,2′,4,4′,5,5′-Hexachlorobiphenyl, 2-(5-Carboxypentanoylamino)-4,4′-dichlorobiphenyl,Biphenyl derivative,4-chlorophenoxyacetic acid,2-Chlorophenoxyacetic acid, DDT,1,1,1-trichloro-2, 2-bis-(p-chlorophenyl)ethane,DDE,1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene,p-Chlorophenol, 4-Chlorophenol, m-Chlorophenol 3,4-Dichlorophenol, 3,5-Dichlorophenol, 2,3,4-Trichlorophenol, 2,3,5-Trichlorophenol, 3-methylindole, 3-methylindole Derivatives, 4-(3-methylindol-5-yloxy)butanoic acid, 4-(3-methylindol-5-yloxy)butanoic acid, 3-methylindole Derivatives, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 6-[n-3-methylindol-5-yloxy carbonyl)amino]hexanoic acid, 3-methylindole Derivatives, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 2-[4-(3-methylindol-6-yl)but-1-ylthio]acetic acid, 3-methylindole Derivatives, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 4-(3-methylindol-6-yl-4-oxo)butanoic acid, 3-methylindole Derivatives, 6-(3-methylindol-7-yloxy)hexanoic acid, 6-(3-methylindol-7-yloxy)hexanoic acid, Indole, Indole-3-Carboxylic acid, Indole Derivative -Indole-3-Acetic acid, Indole-3-Acetic acid, Indole Derivative - Indole-3-Propionic acid, Indole-3-Propionic acid, Indole Derivative-Indole-3-Carbinol,Indole-3-Carbinol, Tryptophan, Tryptamine, 5-Methoxyindole-3-carboxaldehyde,5-Methoxytryptamine,5-Methoxyindole, 6-Methoxyindole, 7-Methoxyindole,EB 1089(Seocalcitol),EB 1089(Seocalcitol) Derivative,(22E,24E)-Des-A,B-24-homo-26,27-dimethyl-8-[(E)-N-(2-carboxyethyl)-carbamoylmethylidene]-cholesta-22,24-dien-25-ol, 1 alpha-25-dihydroxyvitamin D3, 25(OH)D3,25-hydroxyvitamin D3,24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3, Vitamin D2,ergocalciferol,Vitamin D3, cholecalciferol,EB 1446,EB 1436,EB 1445,EB 1470, DeethylHydroxyAtrazine(DEHA) (Structurally related s- triazines), Irgarol 1051, Flourescein Isothiocyanate, FITC,Metanephrine,NorMetanephrine, Propazine, Terbutylazine, Terbuthylazine, 6-chloro-N-(1,1-dimethylethyl)-N′-ethyl-1,3,5-triazine-2,4-diamine, (Structurally related s-triazines),Ametryn (2-Ethylamino-4-isopropylamino-6-methylthio-1,3,5-triazine (Modification iPr/SCH3/Et R1= (CH3)2-CH-NH- R2= -SCH3 R3= -NH-CH2-CH3, Irgarol, Cyanazine ( Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCN(CH3)2 ), OH-Terbutylazine, Terbutylazine-2OH, Hydroxytriazine (EQ-0027), Deisopropylatrazine (Structurally related S-triazine), Desethylterbutylazine (Structurally related S-triazine), Desethyl-deisopropylatrazine (Structurally related S-triazine), Atraton, Terbutryn (Structurally related s-triazines), Atrazine derivative ( Modification R1= -NHCH(CH3)2 R2= -S(CH2)2COOH R3= -NHC2H5), Cyanuric chloride, Trifluralin, (Structurally related s-triazines) tBu/C4/SCH3 ( Modification R1= -NH-C-(CH3)3 R2= -NH(CH2)3COOH R3= -SCH3), Sulphamethazine, (Structurally related s-triazines) 6-[[[4-Chloro-6-(methylamino)]-1,3,5-triazin-2-yl]amino]hexanoic Acid (Modification Me/Cl/C6 R1= -NHCH3 R2= -C1 R3= -NH(CH2)5COOH), (Structurally related s-triazines) Procyazine (Modification R1= -Cl R2= -NHcyclopropyl R3= -NHCCN(CH3)2), (Structurally related s-triazines), Prometon ( Modification R1= -OCH3 R2= -NHCH(CH3)2 R3= -NHCH(CH3)2); (Structurally related s-triazines) Atrazine Mercapturic Acid (AM) (Modification R1= -SCH2CH(NHAc)COOH R2= -NHCH2CH3 R3= -NHCH(CH3)2), (Structurally related s-triazines),desethyl atrazine mercapturic acid (desethyl AM) ( Modification R1= -NAcCys R2= -NH2 R3= -NHCH(CH3)2), (Structurally related s-triazines), deisopropyl atrazine mercapturic acid (deisopropyl AM) (Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NH2), (Structurally related s-triazines), didealkylated atrazine mercapturic acid (didealkylated AM) (Modification R1= -NAcCys R2= -NH2 R3= -NH2), (Structurally related s-triazines), simazine mercapturate ( Modification R1= -NAcCys R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -S(CH2)2COOH R2= -NHCH2CH3 R3= -NHCH2CH3), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH(CH3)2 R3= -NH(CH2)2COOH), (Structurally related s-triazines) (Modification R1= -Cl R2= -NHCH2CH3 R3= -NH(CH2)2COOH), (Structurally related s-triazines), atrazine mercapturic acid methyl ester (AM methyl ester) (Modification R1= -NAcCysME R2= -NHCH2CH3 R3= -NHCH(CH3)2), N-acetylcysteine, S-benzyl mercapturate, (Structurally related s-triazines), simetryn ( Modification R1= -SCH3 R2= -NHCH2CH3 R3= -NHCH2CH3), Metribuzin, 4-amino-6-tert-butyl-4,5-dihydro-3-methylthio-1,2,4-triazin-5-one, Sulpha Drugs, N4-acetyl-sulphamethazine (Modification N4-acetyl-sulphamethazine ), Sulpha Drugs, Sulphathiazole, Sulphathiazole, Sulphamerazine, Sulphamerazine, Sulphaquinoxaline, Sulphaquinoxaline Sulphachlorpyridazine, Sulphachlorpyridazine, Sulphapyridine, Sulphadimethoxine, Sulphadimethoxine, Sulphamethoxazole, Sulphamethoxazole, Sulphisoxazole, Sulphisoxazole, Sulphamethizole, Sulphamethizole, Sulphanilamide, Sulphanilamide, Sulphaguanidine, Sulphaguanidine, Sulphadiazine, Sulphadiazine, Sulphamethoxypyridazine, Sulphamethoxypyridazine, Pentachlorophenoxypropionic acid, Pentachlorophenol, PCP, 2,3,5,6-Tetrachlorophenol, 1,2,4,5 Tetrachlorobenzene, 2,4,6 Trichlorophenol, 2-Methoxy-3,5,6-trichloropyridine, 1,3,5 Trichlorobenzene, 1,3 Dichlorobenzene, 2,4,5-Trichlorophenol, 2,6-Dichlorophenol, 3,5,6-Trichloro-2-pyridinoxyacetic acid, 3,5,6-Trichloro-2-Pyridinol, TCP, 2,4-Dichlorophenol, 2,5-Dichlorophenol, DNC, 4,4′-dinitrocarbanilide, (Structurally related s-triazines), Dichloroatrazine, (Structurally related s-triazines), Dichlorosimazine,, 1-((6-chloropyridin-3-yl)methyl)imidazolidin-2-imin, Pyridine Derivative, 6-chloropyridine-3-carboxylic acid, Nicotinic acid, Pyridine Derivative, N-((6-chloropyridin-3-yl)methyl)-N-methylacetamide, (6-chloropyridin-3-yl)-N-methylmethanamine, (6-chloropyridin-3-yl)methanol, Imidacloprid, 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, Acetamiprid, (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine, Nitenpyram, Deltamethrin, 1(R)-cis-alpha(S)-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid cyano(3-phenoxyphenyl)methyl ester, DON, deoxynivalenol, DON derivative, 15-AcDON (15-acetyldeoxynivalenol), DON derivative, 3-AcDON (3-acetyldeoxynivalenol), DON derivative, 3,15-DiacDON (3,15-diacetyldeoxynivalenol), DON derivative, 3,7,15-TriacDON (3,7,15-Triacetyldeoxynivalenol), NIV (nivalenol), nivalenol, NIV Derivative, 4-AcNIV (fusarenon X), Flutolanil, alpha,alpha,alpha-trifluoro-3′-isopropoxy-o-toluanilide, Mepronil, Mebenil, Benodanil, 24,25(OH)2D3, (24R)-24,25-dihydroxyvitamin D3, 24S,25(OH)2D3, 24S,25-dihydroxyvitamin D3, 25R,26(OH)2D3, 25R,26-dihydroxyvitamin D3, 25S,26(OH)2D3, 25S,26-dihydroxyvitamin D3, 1,24,25(OH)3D3, 1,24,25-trihydroxyvitamin D3, 1,25-lactone, (23S,25R)-1,25(OH)2 D3 26,23-lactone, 24,25(OH)2--7-DHC, 24,25(OH)2--7-dehydrocholesterol, 25(OH)D3 3S, 25(OH)D3 3-sulfate, 24,25(OH)2D3 -Hemiglutarate Derivative, 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3, 24,25(OH)2D3 - Hemiglutarate Derivative, (24R)-24,25-dihydroxyvitaminD3 -3-hemiglutarate, 24R,25(OH)2D2, 24S,25(OH)2D2, 25(OH)D2, 1,24(OH)2D3, 2,3,6-Trichlorophenol, Tetrachlorohydroquinone, Pentachloroaniline, Pentachlorobenzene, 2,3-Dinitrotoluene,,4-Dinitrotoluene, 2,4,5-Trichloronitrobenzene, 3-(3-Hydroxy-2,4,6-trichlorophenyl)-propanoic acid, 2,3,4,6-Tetrachlorophenol, 2,4,6-Trichloroanisol, 2,4,6-TCA, Pentabromophenol, PBP, 2,4,6-Tribromophenol, 2,4,6-TBP, 2-Bromo-4-Chlorophenol, 2-B-4-CP 2,4-Dibromophenol, 2,4-DBP, 2,6-Dibromophenol, 2,6-DBP, 4-Bromophenol, 4-BP, Furosemide, Ampicillin, Amoxicillin, 6-amino-penicillanic acid (6-APA), Azlocillin, Bacampicillin, Carbenicillin, Epicillin, Cloxacillin, Dicloxacillin, Metampicillin, Methicillin, Moxalactam, Oxacillin, Penicillin G, benzyl penicillin, Penicillin V, phenoxy methyl penicillin, Pheneticillin, Piperacillin, Ticarcillin, Ampicillin hydrolyzed, Penicillin G hydrolyzed, 3-phenoxybenzoic acid (3-PBAc) Chlorpyrifos, Chlorpyrifos derivatives, HC101, Synthesized directly from chlorpyrifos technical grade by substitution of the chlorine in position 6 by a 3-mercaptopropanoic acid spacer arm, Chlorpyrifos derivatives, HTCP (Modification HTCP of TCP metabolite was prepared from HC101 by hydrolysis of the thiophosphate ester), Zeatin Riboside (trans isomer), Zeatin (trans isomer), N6-(2-isopentenyl)-adenosine, IPA, N6-(2-isopentenyl)-adenine, 2-iP, Benzyladenine, Kinetin, monuron, monolinuron, fenuron, neburon, propanil, propham, chloropropham, 4-chloroaniline, Methyl Urea Derivative, 1-(3-Carboxypropyl)-3-(4-chlorophenyl)-1-methylurea, Methyl Urea Derivative, 1-(5-Carboxypentyl)-3-(4-chlorophenyl)-1-methylurea, metobromuron, Sennoside B, SB, Sennoside B possessed a erythro configuration between C-10 and C-10′, Sennoside A (Modification Sennoside A possessed a threo configuration between C-10 and C-10′), Rhein, Emodin, Aloe-emodin, Barbaloin, 1,4 Dihydroxyanthraquinone, Rhaponticin, Galic acid, Vanillic acid, Caffeic acid, Homogentisic acid, Esculin, Cinnamtannin B1, Baicalin, Naringin hydrate, Wogonin, Wogonin 7-o-beta-glucuronide, Curcumin, delta1-Tetrahydrocannabinolic acid, delta1-Tetrahydrocannabinol, (+-)-cis-4-Aminopermethrin, 3-(4-Aminophenoxy)benzyl(+-)-cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, Permethrin, trans-Permethrin, cis-Permethrin, Cypermethrin, Phenothrin, Resmethrin, Cyfluthrin, trans-Permethrin acid Esfenvalerate, Fluvalinate, Fenpropathrin, cis-permethrin acid, 4-Phenoxybenzoyl alcohol, Diuron Derivative, 1-(3-Carboxypropyl)-3-(3,4-dichlorophenyl)-1-methylurea, Siduron, Terbuthiuron, Barban, acid trifluralin, 2,6-dinitro-N--propyl-N-(2-carboxyethyl)-4-(trifluoromethyl)benzenamine, TR-13, 2-ethyl-7-nitro-1-propyl-5-(trifluoromethyl)-1H-benzimidazole, benefin, 2,6-dinitro-N-butyl-N-ethyl-4-(trifluoromethyl)benzenamine, TR-2, 2,6-dinitro-N-propyl-4-(trifluoromethyl)benzenamine, ethalfluaralin, 2,6-dinitro-N-ethyl-N-(2-methyl-2-propenyl)-4-(trifluoromethyl)benzenamine, TR-40, N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-N-propylpropanamide, TR-15, 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole, TR-3, 2,6-dinitro-4-(trifluoromethyl)benzenamine, TR-6, 3-nitro-5-(trifluoromethyl)-1,2-benzenediamine, TR-9, 5-(trifluoromethyl)-1,2,3-benzenetriamine, TR-21, 4-(dipropylamino)-3,5-dinitrobenzoic acid, TR-36M, 3-methoxy-2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine, oryzalin, 3,5-dinitro-4-(dipropylamino)benzenesulfonamide, pendimethalin, 2,6-dinitro-N-(1-ethylpropyl)-3,4-dimethylbenzenamine, penta galloyl glucose, Pyrene Pyrene-1-carboxaldehyde, Phenanthrene, Benzo(a)pyrene, 3,4-Benzopyrene, Anthracene, 3,4-Benzopyrene, Acenaphthene, Fluorene, Chrysene, 1,2-Benzphenanthrene, Benzo[g,h,i]perylene, Benzo[e]pyrene, Acenaphthylene, Fluoranthene, Benzo(j,k)fluorene, Indeno-1,2,3-cd-pyrene, 1,10-(1,2-Phenylene)pyrene, Benzo[a]anthracene, 1,2-Benzanthracene, Benzo(k)fluoranthene, Naphthalene, Benzo[a]fluoranthene, Dibenzo[ah]anthracene, 1,2:5,6-Dibenzanthracene, 2,3-Diaminonaphthalene, 2,6-Dinitroaniline, 17-beta-estradiol (ED), estra-1,3,5(10)-triene-3,17-beta-diol, Trifluralin derivative, 2,6-dinitro-4-trifluoromethylaniline, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-methyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-N-propyl-6-aminohexanoic acid, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid methyl ester, Trifluralin derivative, N-(2,6-dinitro-4-trifluoromethylphenyl)-6-aminohexanoic acid tert-butyl ester, Benfluralin, Ethalfluralin, Trifluralin derivative, 2,6-Dinitro-4-trifluoromethylphenol, Isopropalin, Aniline, 2-Hydroxybenzotrifluoride, N-propyl-6-aminohexanoic acid, N-methyl-6-aminohexanoic acid, MHPG Derivatives, D-MHPG (D-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, L-MHPG (L-3-methoxy-4-hydroxyphenylglycol), MHPG Derivatives, DL-MHPG (DL-3-methoxy-4-hydroxyphenylglycol), Isomeric mixture of D-MHPG and L-MHPG forms, MHPG Derivatives, DL-MHPG-SO4 (DL-3-methoxy-4-hydroxyphenylglycol-sulfate) Modification can include Isomeric mixture of D-MHPG-SO4 and L-MHPG-SO4 forms, Serotonin, 5-HT, 5-hydroxydopamine (5-4HDA), 3,4-dihydroxyphenylglycol (DOPEG), Dopamine, 4-(2-aminoethyl)pyrocatechol; 3-hydroxytyramine; 3,4-dihydroxyphenethylamine;, L-3,4-dihydroxyphenylalanine, L-DOPA, Vanillomandelic acid, DL-VMA, Homovanillic acid, Norepinephrine, DL-NE, D-Epinephrine, D-E, 3-methoxytyramine, MTA, 3-methoxytyrosine, MTyr, 3,4-dihydroxymandelic acid, DL-DOMA, 3,4-dihydroxyphenyl acetic acid, DOPAC, L-Phenylalanine, Tyramine, p-tyramine; 4-(2-Aminoethyl)phenol, D-Mandelic acid, Homocatechol, Octopamine, DL-Octopamine, Azinphos-Ethyl, S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl) O,O-diethyl phosphorodithioate, Phosmet, O,O-dimethyl S-phthalimidomethyl phosphorodithioate, Folpet, N-[(Trichloromethyl)thio]phthalimide, Tetramethrin, (1-Cyclohexene-1,2-dicarboximido)methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylate, N-(bromomethyl)phthalimide, N-(Chloromethyl)benzazimide, 6-(N-phthalimidoylmethylthio)hexanoic acid(MFH), Bromacil, 5-bromo-3-sec-butyl-6-methyluracil, Bromacil Derivative, 5-bromo-6-(hydroxymethyl)-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidineone, Bromacil Derivative, 5-bromo-3-(2-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione, Metabolite of Bromacil, Bromacil Derivative, 3-hydroxy-1-methylpropyl-6-methyl-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Bromacil Derivative, 6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Metabolite), Terbacil Derivative, [5-chloro-3-(1,1-dimethylethyl)-6-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione, Terbacil, 3-tert-butyl-5-chloro-6-methyluracil, Bromacil Derivative, Ethyl-5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoate, Bromacil Derivative alkylated at N-1, Bromacil Derivative 5-(5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-1-yl)hexanoic Acid (Modification Bromacil Derivative alkylated at N-1), Bromacil Derivative, -Bromo-6-(Bromomethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative -[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]-2-carboxylpropanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), 3-[5-Bromo-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione-6-yl]propanoic Acid (Modification Bromacil Derivative substituted at the 6-methyl position), Bromacil Derivative 5-Bromo-1,6-dimethyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Bromacil Derivative 5-Bromo-1-butyl-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, Butachlor, N-butoxymethyl-2-chloro-2’,6′-diethylacetanilide, Amidochlor, N-[(acetylamino)methyl]-2-chloro-N-(2,6-diethylpenyl)acetamide, Nicarbazin, N,N′-bis(4-nitrophenyl)-compound with 4,6-dimethyl-2(1H)-pyrimidinone (Modification (DNC + HDP) ), 2-hydroxy-4,6-dimethylpyrimidine, HDP, Imazalil, [1-(beta-allyloxy-2,4-dichlorophenethyl)imidazole], Imazalil Derivative, EIT-0073 (Modification Have a -O(CH2)5-COOH group instead of original -OCH2CH=CH2 group of imazalil), Penconazole, (RS)-1-(2,4-dichloro-β-propylphenethyl)-1H-1,2,4-triazole, Hexaconazole, (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol, Propiconazole, cis-trans-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, Diclobutrazol, 2RS,3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol, Triflumizole, (E)-4-chloro-α,α,α-trifluoro-N-(1-imidazol-1-yl-2-propoxyethylidene)-o-toluidine, Imazalil Derivative, EIT-0183, Imazalil Derivative, EIT-0180, Imazalil Derivative, EIT-0111, Imazalil Derivative, EIT-0158, Imazalil Derivative, K-240, Chlorothalonil, tetrachloroisophthalonitrile Modification On benzene Ring R1 = CN R2 = Cl R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,4,5,6-tetrachloro-3-cyanobenzamide (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = CN R4 = Cl R5 = Cl R6 = Cl), Chlorothalonil Derivative-2,5,6- trichloro-4-hydroxyisophthalonitrile (Modification On benzene Ring R1 = CN R2 = C1 R3 = CN R4 = OH R5 = Cl R6 = Cl), 3-carbamyl-2,4,5-trichlorobenzoic acid (Modification On benzene Ring R1 = CONH2 R2 = C1 R3 = COOH R4 = H R5 = Cl R6 = Cl), Pentachloronitrobenzene (Modification On benzene Ring R1 = NO2 R2 = C1 R3 = Cl R4 = C1 R5 = Cl R6 = Cl), Benzene hexachloride, Hexachlorobenzene, BHC, Lindane (Modification On benzene Ring R1 = C1 R2 = C1 R3 = C1 R4 = Cl R5 = Cl R6 = Cl), 2,4,5,6-tetrachlorophenol (Modification On benzene Ring R1 = OH R2 = C1 R3 = H R4 = Cl R5 = Cl R6 = C1 ), Carbaryl Derivative, Ethylcarbamate (Modification R1 = OCONHCH2CH3 R3 = H), 1-Naphthol, 1-naphthaleneacetamide, -(1-naphthyl)acetamide, Carbaryl Derivative, 1-Methylcarbonate (Modification R1 = OCOOCH3 R2 = H, Carbaryl Derivative, 1-Ethylcarbonate (Modification R1 = OCOOCH2CH3 R2 = H), Carbaryl Derivative 2-Ethylcarbonate (Modification R1 = H R2 = OCOOCH2CH3, Carbaryl Derivative, 1-Ethylthiocarbonate (Modification R1 = OCOSCH2CH3 R2 = H), Carbaryl Derivative, 2-Ethylthiocarbonate (Modification R1 = H R2 = OCOSCH2CH3), Naptalam, N-1-naphthylphthalamic acid, Carbaryl Derivative, 3-hydroxycarbaryl(Modification R1 = OCONHCH3 R2 = H R3 = OH R4 = H R5 = H), Carbaryl Derivative 4-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = OH R5 = H), Carbaryl Derivative 5-hydroxycarbaryl (Modification R1 = OCONHCH3 R2 = H R3 = H R4 = H R5 = OH), Carbaryl Derivative, 1-(5-Carboxypentyl)-3-(1-naphthyl)urea (Modification R1 = NHCONH(CH2)5COOH R2 = H), (Structurally related s-triazines) -Aziprotryn, 4-azido-N-isopropyl-6-methylthio-1,3,5-triazin-2-ylamine (Modification R1 = -SCH3 R2 = -N3 R3 = -CH(CH3)2), (Structurally related s-triazines), 2-(ethylamino)-4-(methylthio)-6-aminotriazine (Modification R1 = -SCH3 R2 = -NH-C2H5 R3 = -NH2), (Structurally related s-triazines) -2-amino-4-(methylthio)-6-(isopropylamino)triazine (Modification R1 = -SCH3 R2 = -NH2 R3 = -NH-CH(CH3)2), (Structurally related s-triazines) - 2-amino-4-methoxy-6-(isopropylamino)triazine (Modification R1 = -OCH3 R2 = -NH2 R3 = -NH-CH(CH3)2 ), TCP Derivative (3,5,6-trichloro-2-pyridinol Derivative), 3-(3,5-dichloro-6-hydroxy-2-pyridyl)thiopropanoic Acid, p-nitrosuccinanilic acid (PNA-S), PNA-S, PNA-C, p-nitro-cis-1,2-cyclohexanedicarboxanilic acid, Nitroaniline Derivative, 2-nitroaniline, o-Nitroaniline, Nitroaniline Derivative- 3-nitroaniline, m-Nitroaniline, Nitroaniline Derivative - 4-nitroaniline, p-Nitroaniline, Aeromatic Alcohols, 4-nitrobenzyl alcohol, Aeromatic Alcohols - 4-nitrophenethyl alcohol, Aeromatic Alcohols 2-nitrobenzyl alcohol, Aeromatic Alcohols, 3-nitrobenzyl alcohol, Urea Derivative-1-benzyl-3-(4-nitrophenyl)urea, Urea Derivative- 1-(3-chlorophenyl)-3-(2-methoxy-5-nitrophenyl)urea, Urea Derivative - 1-(3-chlorophenyl)-3-(4-methoxy-3-nitrophenyl)urea, Urea Derivative - 1-(4-chlorophenyl)-3-(4-nitrophenyl)urea, Urea Derivative -(2-fluorophenyl)-3-(2-mehtoxy-4-nitrophenyl)urea, 1-(3-mehtoxyphenyl)-3-(3-nitrophenyl)urea, Carbofuran Derivative m Carbofuran-phenol, Carbofuran-hydroxy, Carbofuran-keto, Carbosulfan,,3-dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate, Benfuracarb, N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate, Furathiocarb, 2,3-dihydro-2,2-dimethyl-7-benzofuranyl 2,4-dimethyl-5-oxo-6-oxa-3-thia-2,4-diazadecanoate, Carbofuran Derivative, 4-[[(2,3-Dihydro-2,2-dimethyl-7-benzofuranyloxy)carbonyl]-amino]butanoic Acid (BFNB) (Modification n = 3 X = CH2), Endrin, nendrin, (1R,4S,4aS,5S,6S,7R,8R,8aR)-1,2,3,4,10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene, Heptachlor, 1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-, Chlordane, 1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methanoindene, Endosulfan (Modification isomer mix of alpha and beta forms), Endosulfan (Modification alpha isomeric form), Endosulfan (Modification beta isomeric form), Endosulfan Derivative, Endosulfan sulfate (Modification sulfate form), Endosulfan Derivative, Endosulfan diol, Diol metabolite of endosulfan, Endosulfan Derivative, Endosulfan ether (Modification ether metabolite of endosulfan), Endosulfan Derivative, hydroxy ether, hydroxy ether metabolite of endosulfan, Endosulfan Derivative, Endosulfan lactone (Modification lactone metabolite of endosulfan), Aldrin, Dieldrin, Fenvalerate isomers Modification 1S,2R isomer R : Ph), Fenvalerate isomers (Modification 1R,2S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R isomer R : Ph), Fenvalerate isomers (Modification 1S,2R/S isomer R : Ph), Fenvalerate isomers (Modification 1R,2R/S isomer R : Ph), Fenvalerate isomers, fenvalerate (Modification 1R/S,2R/S isomer R : Ph), Thiabendazole, 2-(thiazol-4-yl)benzimidazole, Thiabendazole Derivative, 5-hydroxythiabendazole (Modification 5-OH-TBZ), Thiabendazole Derivative, 5-NH2-TBZ, Thiabendazole Derivative, methyl benzimidazole carbamate, Albendazole, Mebendazole, Fenbendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Thiabendazole Derivative, 2-succinamidothiabendazole, Cambendazole, Fenvalerate Haptens, Cyano[3-(4-aminophenoxy)phenyl]methyl (S)-4-Chloro-alpha-(1-methylethyl)benzeneacetate (4-Aminoesfenvalerate), Fenvalerate Haptens, Benzyl 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoate, Fenvalerate Haptens, Benzyl 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetate, Fenvalerate Haptens, 3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxyacetic Acid, Fenvalerate Haptens, Benzyl 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoate, Fenvalerate Haptens, 6-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]hexanoic Acid Fenvalerate Haptens, 4-[3-[Cyano[(S)-2-(4-chlorophenyl)-3-methyl-1-oxobutanoxy]methyl]]phenoxy]benzenepropanoic Acid, (S)-fenvalerate Acid, (Structurally related s-triazines), atrazine mercapturate Modification R1 = -SCH2CH(NHCOCH3)COOH R2 = -NHCH2CH3 R3 = -NHCH(CH3)2, Fenthion Hapten, -Methyl O-[3-methyl-4-(methylthio)phenyl] N-(3-carboxypropyl)phosphoramidothioate Modification referred as Hapten B, Fenthion Derivative, Oxidized Fenthion, Fenthion Derivative, Oxidized oxidized Fenthion, pirimiphos-ethyl, 4-(Methylthio)-m-cresol, Chlorpyrifos Derivative, Chlorpyrifos-oxon, Fenchlorphos, O,O-dimethyl O-2,4,5-trichlorophenyl phosphorothioate, Trichloronate, O-Ethyl O-2,4,5-trichlorophenyl ethyl-phosphonothioate, Dichlofenthion, O-2,4-dichlorophenyl O,O-diethyl phosphorothioate, Parathion, O,O-diethyl O-4-nitrophenyl phosphorothioate ; Thiophos, Chlorpyrifos Derivative Modification Synthesis of AR1 is described, Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) O-(3-Carboxypropyl)Phosphorothioate;(PO), Chlorpyrifos Derivative - O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(5-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of thiophosphate reagents), Chlorpyrifos Derivative, O-Ethyl O-(3,5,6-Trichloro-2-pyridyl) N-(2-Carboxyethyl)Phosphoramidothioate;(PN1) (Modification Amide linkage of suitable thiophosphate reagents ),, Triadimefon, (RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, GR151004, (4-[[5-[3-[2-(dimethylamino)ethyl]]-5-benzofuranyl]-3-pyridinyl]acetyl]morpholine dihydrochloride, Diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, (Structurally related s-triazines) - SprAAT (Modification R1 = SCH2CH2COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SBeAAT (Modification R1 = S(C6H4)COOH R2 = NH2 R3 = NH2), (Structurally related s-triazines), SAAT (Modification R1 = SH R2 = NH2 R3 = NH2), (Structurally related s-triazines), CDAT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH2), (Structurally related s-triazines)- CDET (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH2CH3), (Structurally related s-triazines) - CDIT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH(CH(CH3)2)), (Structurally related s-triazines), CDDT (Modification R1 = Cl R2 = NH[C(O)CH3) R3 = NH[C(O)CH3)), (Structurally related s-triazines) - ammeline, OAAT(Modification R1 = OH R2 = NH2 R3 = NH2), (Structurally related s-triazines)- ammelide, OOAT (Modification R1 = OH R2 = OH R3 = NH2), (Structurally related s-triazines) - cyanuric acid, OOOT (Modification R1 = OH R2 = OH R3 = OH), (Structurally related s-triazines), melamine, AAAT (Modification R1 = NH2 R2 = NH2 R3 = NH2), Structurally related s-triazines- N-isoropylammeline, OIAT ( Modification R1 = OH R2 = NH[CH(CH3)2] R3 = NH2, Structurally related s-triazines - N-ethylammeline, OEAT (Modification R1 = OH R2 = NHCH2CH3 R3 = NH2), Structurally related s-triazines, N-ethylammelide, OOET (Modification R1 = OH R2 = OH R3 = NHCH2CH3), Structurally related s-triazines)- cyromazine,CyPAAT (Modification R1 = NH(C3H5) R2 = NH2 R3 = NH2), Structurally related s-triazines - diamino-s-triazine,, HAAT( Modification R1 = H R2 = NH2 R3 = NH2), PCB congeners, 2,5,3′,4′-tetrachlorobiphenyl (Modification IUPAC no. : 70), PCB congeners
- 2,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC no. : 118), PCB congeners - 2,2′,5,5′-tetrachlorobiphenyl (Modification IUPAC no. : 52), PCB congeners, 6-[3,3′,4′-Trichlorobiphenyl-4-yl)oxy]hexanoic Acid, Metolazone, Brand Names : Mykrox; Zaroxolyn, Furfuryl benzoate, DDT Metabolites, DDA, Paraquat, 1,1′-dimethyl-4,4′-bipyridinium ion, Diethylcarbamazine, THP, 2,4,6-triphenyl-N-(4-hydroxyphenyl)-pyridinium, o-DNCP, -dinitrocarboxyphenol, PCB congeners, 3-chlorobiphenylol (Modification IUPAC No. 2), PCB congeners, 3,4′-dichlorobiphenyl (Modification IUPAC No. 13),PCB congeners, 3,5-dichlorobiphenyl (Modification IUPAC No. 14), PCB congeners, 3,4,5,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 126), 2,3,3′,4′-tetrachlorobiphenyl (Modification IUPAC No. 56), 2′,3,4,5-tetrachlorobiphenyl (Modification IUPAC No. 76), 3,3′,5,5′-tetrachlorobiphenyl (Modification IUPAC No. 80), 2,4,5,2′,5′-pentachlorobiphenyl (Modification IUPAC No. 101), 2,3,3′,4,4′-pentachlorobiphenyl (Modification IUPAC No. 105), 2,3,6,3′,4′-pentachlorobiphenyl (Modification IUPAC No. 110), 3,3′,4,5,5′-pentachlorobiphenyl (Modification IUPAC No. 127), 3,4,5,3′,4′,5′-hexachlorobiphenyl (Modification IUPAC No. 169 ), 2,3,3′,4,4′,5-hexachlorobiphenyl (Modification IUPAC No. 156), 3,4,3′,4′-tetrabromobiphenyl, 3,4,5,3′,4′,5′-hexabromobiphenyl, 2,4,5,2′,4′,5′-hexabromobiphenyl, Dibenzofurans and Dioxins, 2,3,7,8-tetrachlorobenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3,4′,5-trichloro-4-biphenylol, 3,3′,5,5′-tetrachloro-4,4′-biphenyldiol, 3,4,3′,4′-tetrachlorodiphenyl ether, 1-2-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 3,4-dichloroaniline, DDT Metabolites, 4,4′-DDT, 4,4′-DDD Retronecine, 3,4-dichlorobiphenyl Modification IUPAC No. 12,, 3,4,3′-trichlorobiphenyl (Modification IUPAC No. 35), PCB Congeners, 3,4,4′-trichlorobiphenyl (Modification IUPAC No. 37), 3,4,3′,5-tetrachlorobiphenyl (Modification IUPAC No. 78), 3,4,3′,5′-tetrachlorobiphenyl (Modification IUPAC No. 79), 3,4,4′,5-tetrachlorobiphenyl (Modification IUPAC No. 81), DDT Metabolites, p,p′-DDT (Modification p,p′-dichlorodiphenyltrichloroethane), o,p′-DDT Modification o,p′-dichlorodiphenyltrichloroethane, p,p′-DDE Modification p,p′-DDE, o,p′-DDE Modification o,p′-DDE, p,p′-DDD Modification p,p′-DDD, o,p′-DDD Modification o,p′-DDD, Dicofol, 4,4-dichloro-a-(trichloromethyl)benzhydrol, Cyprazine, 6-chloro-N-cyclopropyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, Structurally related s-triazines, Dipropetryn, 6-(ethylthio)-N,N′-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine, Trietazine, 6-chloro-N,N,N′-triethyl-1,3,5-triazine-2,4-diamine, 6-Hydroxyatrazine, hexazinone, 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione, TNT, 2,4,6-Trinitrotoluene, Tetraconazole (M14360), 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, DTP, 2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, Imazalyl, fenarimol, (RS)-2,4′-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol, Lupanine metabolites, (+)-lupanine (Modification R = H), Lupanine metabolites, (+)-13-hydroxylupanine (Modification R = OH ), Lupanine metabolites, hemisuccinate ester of (+)-13-hydroxylupanine (Modification R = OCO-(CH2)2.COOH), Lupanine metabolites, cis-hexahydrophthalate ester of (+)-13-hydroxylupanine (Modification R = OCO.C6H10.COOH ),, Lupanine metabolites, alpha-isolupanine, Lupanine metabolites, -hydroxylupanine, Sparteine, Cysteine, multiflorine, epilupinine, (Structurally related s-triazines), CYANAZINE ACID Modification R1 = C1 R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2, Structurally related s-triazines Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)3COOH, Structurally related s-triazines (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCH2COOH), (Structurally related s-triazines) (Modification R1 = C1 R2 = NHCH2CH3 R3 = NH(CH2)4COOH), norflurazon, 4-chloro-5-(methylamino)-2-[3-(trifluoromethyl)phenyl]-3(2H)-pyridazinone, norflurazon derivative, desmethyl-norflurazon, metflurazon, -chloro-5-(dimethylamino)-2-[(3-trifluoromethyl)phenyl]-3(2H)-pyridazinone, Pyrazon, Chloridazon, 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone (active ingradient), dichlorophenyl-pyridazone, (Structurally related s-triazines) azidoatrazine (Modification R1 = N3 R2 = NHCH(CH3)2 R3 = NHCH2CH3), ALACHLOR 2-chloro-2′,6′-diethyl-N-methoxymethylacetanilide, trichothecolone (Modification R1 = H R2 = OH R3 = H R4 = O R5 = H), DON derivative, acetyl-T-2, DON derivative, T-2 tetrol tetraacetate, Chlorpyrifos derivatives, mono-dechloro-CP, Bromophos derivative, Bromophos-methyl, Bromophos derivative, Bromophos-ethyl dicapthon, -2-chloro-4-nitrophenyl O,O-dimethyl phosphorothioate, tetrachlorvinphos, (Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate, triclopyr, 3,5,6-trichloro-2-pyridyloxyacetic acid, picloram, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, Formononetin, Biochanin A, 5, 7-dihydroxy-4′-methoxyisoflavone (Modification It is the 4′-methyl ether of genistein), equol, (7-hydroxy-3-(4′-hydroxyphenyl)-chroman, 2′methoxyformononetin, Daidzein, 7-hydroxy-3- (4-hydroxyphenyl)-4H -1-benzopyran-4-one, geninstein, quercetin, 3,3′,4′,5,7-Pentahydroxyflavone; 3,5,7,3′,4′-Pentahydroxyflavone;, matheucinol, coumestrol, (Structurally related s-triazines), Hydroxysimazine (Modification R1 = OHR2 = NHCH2CH3R3 = NHCH2CH3, angustifoline, Alodan, 1 - Methyl - 4 - phenyl - 4 -carboethoxypiperidine hydrochloride, Zearalenone, RAL, F-2 Toxin, Fenpropimorph, (RS)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine, Tridemorph, 2,6-dimethyl-4-tridecylmorpholine, 2,6-dimethylmorpholine, Amorolfine, Fenpropidine, (RS)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]piperidine, (Structurally related s-triazines) (Modification R1 = Cl R2 = Cl R3 = NHCH2CH3, (Structurally related s-triazines) Modification R1 = Cl R2 = C1 R3 = NHCH(CH3)2, (Structurally related s-triazines) Modification R1 = Cl R2 = NHCH2CH3 R3 = NH(CH2)5COOH, (Structurally related s-triazines) Modification R1 = C1 R2 = NHCH(CH3)2 R3 = NHCH2COOH, (Structurally related s-triazines) (Modification R1 = Cl R2 = NHCH(CH3)2 R3 = NH(CH2)5COOH), Structurally related s-triazines, cyanazine amide (Modification R1 = Cl R2 = NHCH2CH3 R3 = NHCCONH2(CH3)2), hydroxycyanazine acid (Modification R1 = OH R2 = NHCH2CH3 R3 = NHCCOOH(CH3)2), deethylsimazine (Modification R1 = Cl R2 = NH2 R3 = NHCH2CH3), Albendazole sulfoxide, [5-(propylthionyl)-1H-benzimidazol-2-yl]-, methylester, Albendazole sulfone, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylthio)benzimidazole, 5(6)-alkylbenzimidazoles, 2-amino-5-(propylsulfonyl)benzimidazole, oxibendazole, 5-propoxy-benzimidazole-2-methyl carbamate, 5(6)-arylbenzimidazoles, fenbendazole sulfone (Modification sulfone metabolite of fenbendazole ), 5(6)-arylbenzimidazoles, 4′-hydroxyfenbendazole, 5(6)-arylbenzimidazoles, oxfendazole (Modification Oxfendazole is the sulfoxide metabolite of fenbendazole), 5(6)-arylbenzimidazoles, flubendazole, benzimidazole Metabolites, 2-aminobenzimidazole, benzimidazole Metabolites, 5-aminobenzimidazole, benzimidazole Metabolites, 2-acetylbenzimidazole, Benzophenone, Diphenylmethanone; phenyl ketone; Diphenyl ketone; Benzoylbenzene, Benzaldehyde, benzoic aldehyde, 4-Bromo-2,5-dichlorophenol, Acephate, O,S-dimethyl acetylphosphoramidothioate, methamidophos, O,S-dimethyl phosphoramidothioate, Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, Phenthoate, S-α-ethoxycarbonylbenzyl O,O-dimethyl phosphorodithioate, EPN, Ethyl p-nitrophenyl thionobenzenephosphonate, Bioresmethrin, -benzyl-3-furylmethyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (Modification The unresolved isomeric mixture of this substance has the ISO common name resmethrin), flufenoxuron, 1-[4-(2-chloro-α,α,α-trifluoro-p-tolyloxy)-2-fluorophenyl]-3-(2,6-difluorobenzoyl)urea, Amitrole, 1H-1,2,4-triazol-3-ylamine, molinate, S-ethyl azepane-1-carbothioate, molinate derivative (Modification S-2-carboxyethyl hexahydroazepine-1-carbothioate ), molinate derivative (Modification S-5-carboxypentyl hexahydroazepine-1-carbothioate) molinate derivative (Modification molinate sulfone), molinate derivative (Modification S-(p-aminobenzyl) hexahydroazepine-1-carbothioate), molinate derivative (Modification S-2-(p-aminophenyl)ethyl hexahydroazepine-1-carbothioate), hexamethylenimine, thiobencarb (Bolero), butylate (Sutan), EPTC (Eptam), cycloate (Roneet), pebulate (Tillam), vernolate (Vernam), Aflatoxin M1, AFM1 (Modification AFM1), Aflatoxin B1, AFB1 (Modification AFB1), Aflatoxin G1, AFG1 (Modification AFG1), Aflatoxin M2, AFM2 (Modification AFM2), Aflatoxin B2, AFB2 (Modification AFB2), Aflatoxin G2, AFG2 (Modification AFG2), Aflatoxin B2alpha, AFB2alpha (Modification AFB2alpha), Aflatoxin G2alpha, AFG2alpha (Modification AFG2alpha), KB-6806, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH(CH3)2 R3 = CH3, Hapten Name KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH2CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NHCOCH3 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = H R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives (Modification R1 = NH2 R2 = CH(CH3)2 R3 = CH3), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = =N(->O) CH3 ( N-OXIDE), KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH(CH3)2 R3 = H, KB-6806 (Benzimidazole ) Derivatives Modification R1 = NH2 R2 = CH2CH3 R3 = CH3, Aminoparaoxon, phosphoric acid, O,O-diethyl O-(4-aminophenyl) ester,Methylparathion, phosphorothioic acid, O,O-dimethyl O-(4-nitrophenyl) ester, Diethyl phenylphosphate, phenylphosphonic acid, O,O-diethyl ester, Diethyl phosphate, ethylphosphonic acid, O,O-diethyl ester, p-Nitorphenyl phosphate, phosphonic acid, O-(4-nitrophenyl)ester, Phorate, phosphorodithioic acid, O,O-diethyl S-[(ethylthio)methyl] ester, Ethion, bis(phosphorodithioic acid), S,S′-methylene O,O,O′,O′-tetraethyl ester, Carbophenthion, phosphorodithioic acid, O,O-diethyl S-[[(4-chlorophenyl)thio]methyl] ester, Disulfoton, phosphorodithioic acid, O,O-diethyl S-[(2-ethylthio)ethyl] ester, TS, N-[4-(Carboxymethyl)-2-thiazolyl)sulfanilamide, NS, N-(4-Nitrophenyl)sulfanilamide, Sulfamoxole, Sulfacetamide, DNP-SL, Spin labelled dinitrophenyl (Modification The synthesis of DNP-SL has been described by Balakrishnan et al(1982) formula can be found in Anglister et al.(1984)), beta ecdysone, Benzimidazole Derivative, 5(6)-[Carboxypentyl)thio]-2-(methoxycarbonyl)amino]-benzimidazole, 2-hydroxybiphenyl, HBP, Atrazine Caproic acid, Lysophosphatidic acid (LPA), 1-acyl-2-hydroxy-sn-glycero-3-phosphate), berberine, Palmatine, 9-Acetylberberine, Corydaline, Coptisine, Berberrubine, 8-Oxoberberine, Papaverine, Berberine Derivative, 9-O-carboxymethyl berberine, phencyclidine, 1-(1-phenylcyclohexyl)piperidine, Methoxychlor, Endosulfan Derivative, 4-Oxobutanoic Acid,4-(4,5,6,7,8,8-Hexachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indenyl-1-oxy), Endosulfan Derivative, 4-oxybutanoic Acid,4-(1,3,4,5,6,7,8-Octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindanyl-2-oxy, Endosulfan Derivative (Modification Hemisuccinate of Endosulfan diol), Triazole Derivatives, 5-(3-Hydroxypropyl)-3-amino-2H-1,2,4-triazole, Triazole Derivatives, 5-(3-Hydroxypropyl)-3-(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole, Triazole Derivatives, 3-Amino-5-[(3-succinyloxy)propyl]-2H-1,2,4-triazole, Triazole Derivatives, 3-amino-1,2,4-triazole-5-thiol, Triazole Derivatives, 3-[(2-nitrophenylsulfenyl)amino-2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 2H-1,2,4-triazole-5-thiol, Triazole Derivatives, 4-methyl-1,2,4-triazole-3-thiol, Triazole Derivatives, (1,2,4-triazol-2-yl)acetic acid, 1,2,4-triazole, 4-nitrophenyl 4′-carboxymethylphenyl phosphate, Triazole Derivative, 4-amino-1,2,4-triazole, Triazole Derivative, 3-acetamido-1H-1,2,4-triazole, Triazole Derivative, 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate, Triazole Derivative, 2-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-methylhexanoic acid, succinic acid, Imidazole, L-histidine, L-glutamic acid, Permethrin derivative, 3-phenoxybenzyl 2,2-dimethylcyclopropane-1,3-dicarboxylate, 3-phenoxybenzaldehyde, flucythrinate, Chrysanthemic acid, 2,4-Dinitrophenyl, DNP, Thiram Haptens, Disodium 4-[Carbodithioato(methyl)-amino]butanoate, Thiram Haptens 5,11-Dimethyl-6,10-dithioxo-7,9-dithia-5,11-diazadodecanoic Acid, Thiram Haptens, 2-{[(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram Haptens, 4-{[(Dimethylamino)carbothioyl]sulfanyl}butanoic Acid, Thiram Haptens, 6-{[(Dimethylamino)carbothioyl]sulfanyl}hexanoic Acid, Thiram Haptens, 11-{[(Dimethylamino)carbothioyl]sulfanyl}undecanoic Acid, Thiram Haptens, 2-{ [(Dimethylamino)carbothioyl]sulfanyl}ethanoic Acid, Thiram, Tetramethylthiurammonosulfide, Tetraethylthiuram disulfide, Dimethyldithiocarbamic acid sodium salt, Dimethyldithiocarbamic acid zinc salt, Diethyldithiocarbamic acid sodium salt, N,N,N′,N′-tetramethylthiourea, Nabam, Zineb, Maneb, Ethylenethiourea, Chlorpyrifos hapten, O,O Diethyl O-[3,5-Dichloro-6-[(2-carboxyethyl)thio]-2-pyridyl] Phosphorothioate, 2-Succinamidobenzimidazole, Methyl 2-Benzimidazolecarbamate, MBC, Benzimidazole, 2-benzimidazolylurea, succinamide, Ethyl carbamate, Urea, N-methylurea, N,N′-dimethylurea, Brevetoxin PbTx-3, Organophosphorous Haptens, O,O-Diethyl O-(5-carboxy-2-fluorophenyl) phosphorothioate, Chlorpyrifos-ethyl, Anandamide hapten, N-Arachidonyl-7-amino-6-hydroxy-heptanoic acid, Anandamide, Arachidonic acid, Docosatetraenoyl ethanolamide, Dihomo-gamma-linolenyl ethanolamide, 2-Arachidonyl glycerol, 2-Arachidonyl glycerol ether, Stearoyl ethanolamide, Heptadecanoyl ethanolamide, Prostaglandin E1, 3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentaneheptanoic acid; alprostadil; PGE1, Prostaglandin D2, PGD2, Prostaglandin A2, PGA2, Prostaglandin B2, PGB2, Prostaglandin F2 alpha, 7-[3,5-dihydroxy-2-(3-hydroxy-1-octenyl)cyclopentyl]-5-heptenoic acid; dinoprost; PGF2alpha, Prostaglandin F1 alpha, PGF1alpha, 6-keto-Prostaglandin F1 alpha, 6-keto-PGF1alpha, 13,14-Dihydro-15-keto-Prostaglandin E2, 13,14-Dihydro-15-keto-PGE2, 13,14-Dihydro-15-keto-Prostaglandin F2alpha, 14-Dihydro-15-keto-PGF2alpha, 5alpha,7alpha-Dihydroxy-11-ketotetranorpostane-1,16-dioic acid, 15-keto-PGF2alpha, TXB2, Prostaglandin E2, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; dinoprostone; PGE2, hCG-alpha-(59-92)-peptide (34 residues), Paraquat Derivative, Paraquat hexanoate (PQ-h), Monoquat, Diquat, 9,10-dihydro-8a,10a-diazoniaphenanthrene, MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, 1,2-Naphthoquinone, N-Acetyl-S-(1,2-dihydroxy-4-naphthyl)cysteine, N-Acetyl-S-(1,4-dihydroxy-2-naphthyl)cysteine, N-Acetyl-S-(1,2-dihydroxy-1-hydroxy-1-naphthyl)cysteine, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid, 2-Chloro-2′.6′-diethylacetanilide(CDA) Hapten, 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid, CDA, 2-Chloro-2′.6′-diethylacetanilide, HDA, 2-Hydroxy-2′.6′-diethylacetanilide, 2,6-diethyl-aniline, Hydroxyalachlor, Alachlor ESA, Alachlor ethanesulfonic acid, Isoproturon Hapten, 3-(4-Isopropylphenyl)-1-carboxypropyl-1-methyl urea, chlorotoluron, 3-(3-chloro-p-tolyl)-1,1-dimethylurea, Metoxuron, 3-(3-chloro-4-methoxyphenyl)-1,1-dimethylurea, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, mecoprop, (RS)-2-(4-chloro-o-tolyloxy)propionic acid, propyzamide, 3,5-dichloro-N-(1,1-dimethylpropynyl)benzamide, Paraquat dichloride, MCPB, 4-(4-chloro-o-tolyloxy)butyric acid, Chlortoluron Hapten, N-(3-Chloro-4-methylphenyl)-N-methyl-N-carboxypropyl Urea, Metsulfuron, Methyl 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)ureidosulphonyl]benzoate, Captopril Haptens, Captopril-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid(MCC), Captopril Haptens, Captopril Disulfide Modification, Mercaptoethanol-MCC, Mercaptoethanol-4-(Maleimidomethyl)-cyclohexane Carboxylic Acid Modification,Captopril Haptens, Captopril without MCC, Aculeatiside A, Aculeatiside B, Solamargine, Solasonine, solanine-S; purapurine, Solasodine, Khasianine, Tomatine, lycopersicin, Tomatidine, 3-O--beta-D-Glucopyranosyl-solasodine, O-alpha-L--Rhamnosyl-1(1->2)-3-O-beta-D-glucopyranosyl-solasodine, 3-O-beta-D-Galacopyranosyl-solasidine, O-beta-D-Glucopyranosyl-1(1->3)-3-O-beta-D-galacopyranosyl-solasodine, 12-Hydroxysolamargine, 12-Hydroxysolasonine, Isoanguivine, Solaverine I, Solaverine II, Xylosyl-beta-solamargine, alpha-Solanine, alpha-Chaconine, Dioscine, Indole Derivatives, beta-Indole Acetic Acid, 2-Bromo-4,6-dinitroaniline, 2-Chloro-4,6-dinitroaniline, Tetryl, 2,4,6-trinitrophenyl-n-methylnitramine, nitramine, tetralite, tetril, 2-Amino-4,6-dinitrotoluene, 2,4-Dinitroaniline, 3,5-Dinitroaniline, 2-Amino-4,6-dinitrobenzoic acid, Disperse Blue 79, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-ethoxyphenyl]acetamide, 1,3-Dinitrobenzene, 2,6-Dinitrotoluene, 4-Amino-2,6-dinitrotoluene, 1,3,5-Trinitrobenzene, Nicergoline, Ethylmorphine,,8-Didehydro-4,5-epoxy-3-ethoxy-17-methylmorphinan-6-ol, Dihydromorphine, Dihydrocodeine, dihydromorphinone, Hydromorphone, Dihydrocodeinone, Hydrocodone, Naltrexone, N-cyclopropylmethyl-14-hydroxydihydromorphinone, Dextromethorphan, (±)-3-Methoxy-17-methylmorphinan, Homatropine, Endorphins Modification Derivative Type: b-Endorphin, Met-enkephalin, DALEA, D-Ala(2)-D-Leu(5)-enkephalinamide, Vincristine, 22-Oxovincaleukoblastine, leurocristine; VCR; LCR, OCT, 22-Oxacalcitriol, OCT-3-HG, 22-oxacalcitriol-3-Hemiglutarate, 24(OH)OCT, 24(OH)-22-oxacalcitriol, 1,20(OH)2-hexanor-D3, Synephrine, Epinephrine, 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]-1,2-benzenediol, Phenylephrine, Dopamine Derivative, 6-hydroxy dopamine, Tyramine derivative, 3-methoxy tyramine, Phenethylamine, Benzeneethanamine; PEA, m-tyramine, o-tyramine, dimethoxyphenethylamine, Thymidine glycol monophosphate, 5,6-Dihydroxythymidine monophosphate, Thymidine monophosphate, Thymidine glycol, Thymine glycol, 5,6-Dihydrothymidine, Thymidine, Thymine, 5-methyluracil; 2,4-dihydroxy-5-methylpyrimidine, AMP, Adenosine mono phosphate, CMP, Cytidine mono phosphate, Carbamazepine, 5-carbamoyl-5H-dibenz[b,f]azepine, Neopterin isomers, D-erythro-Neopterin, Neopterin isomers, L-erythro-Neopterin, Neopterin isomers, D-threo-Neopterin, Biopterin isomers, L-erythro-Biopterin, Biopterin isomers, D-erythro-Biopterin, Biopterin isomers, L-threo-Biopterin, Biopterin isomers, D-threo-Biopterin, Pterin-6-Carboxylic Acid, C7H5NiO3, Pterin, Thromboxane B2, (5Z,9alpha,13E,15S)-9,11,15-trihydroxythromboxa-5,13-dien-1-oic acid, 15 Ketoprostaglandin F2alpha, Fumonisin B1, macrofusine; FB1, Thyroliberin, TRH ; thyrotropin-releasing factor; thyrotropin releasing hormone; TRF; protirelin; lopremone, Thyroliberin-OH, TRH-OH, Diketopiperazine, cyclo (H-P), TRH analogues, Methylated TRH, TRH analogues, TRH elongated peptides, TRH-Gly, TRH elongated peptides, TRH-Gly-Lys-Arg, TRH elongated peptides, TRH-Gly-Lys-Arg-Ala, TRH elongated peptides, P7 (Modification Q-H-P-G-L-R-F), TRH elongated peptides, P10 (Modification S-L-R-Q-H-P-G-L-R-F), TRH elongated peptides, Ps5 Modification pro-TRH[178-199], TRH elongated peptides, TRH-Ps5 (Modification pro-TRH[172-199]), Hypothalmic peptide, LHRH, Cyanoginosin-LA, Cyanoginosin-LB, Cyanoginosin-LR, Cyanoginosin-LY, Cyanoginosin-AY, Cyanoginosin-FR, Cyanoginosin-YR, Ne-acetyllysine-containing peptide, Gly-Lys(Ac)-e-aminocaproic acid (Aca)-Cys, Benzoic Acid, Benzenecarboxylic acid; phenylformic acid; dracylic acid, m-hydroxybenzoic acid, 3-hydroxybenzoic acid, o-methoxybenzoic acid, 2-methoxybenzoic acid, o-toluic acid, 2-Methylbenzoic acid, o-chlorobenzoic acid, 2-chlorobenzoic acid, o-aminobenzoic acid, 2-aminobenzoic acid, thiosalicylic acid, 2-Mercaptobenzoic acid; o-sulfhydrylbenzoic acid, Salicylamide, 2-Hydroxybenzamide, Saligenin, saligenol; o-hydroxybenzyl alcohol; Salicyl alcohol, 2-cyanophenol, 2-hydroxyphenyl acetic acid, p-hydroxybenzoic acid, p-aminobenzoic acid, 4-Aminobenzoic acid; vitamin Bx; bacterial vitamin H1, p-toluic acid, p-methylamino benzoic acid, p-chlorosalicylic acid, 4-chloro-2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, beta-Resorcylic Acid; 2,4-dihydroxybenzenecarboxylic acid; BRA, 4-aminosalicylic acid, 4-Amino-2-hydroxybenzoic acid; p-aminosalicylic acid, Gentisic Acid, 2,5-dihydroxybenzoic acid; 5-hydroxysalicylic acid, Picolinic acid, o-Pyridinecarboxylic acid; 2-Pyridinecarboxylic acid, picolinic acid N-oxide, 3-hydroxypicolinic acid, 2-hydroxynicotinic acid, 7-methylguanine, N2-Carboxymethyl-N7-methylguanine, 2-(7-methyl-6-oxo-6,7-dihydro-1H-purin-2-ylamino)acetic acid, 7-methylxanthine, 7-methyluric acid, 7-methyladenine, Guanine, 2-Amino-1,7-dihydro-6H-purin-6-one; 2-aminohypoxanthine, Adenine, 6-aminopurine; 6-amino-1H-purine; 6-amino-3H-purine; 6-amino-9H-purine, 7-(2-Carboxyethyl)guanine, 7-CEGua, 7-Ethylguanine, 2-amino-7-ethyl-1H-purin-6(7H)-one, 7-(2,3-Dihydroxypropyl)guanine, 2-amino-7-(2,3-dihydroxypropyl)-1H-purin-6(7H)-one, 7-(2-Hydroxyethyl)guanine, 2-amino-7-(2-hydroxyethyl)-1H-purin-6(7H)-one, 7-(2-[(2-Hydroxyethyl)amino]ethyl)-guanine, 2-amino-7-(2-(2-hydroxyethylamino)ethyl)-1H-purin-6(7H)-one, 7-Carboxymethylguanine, or 2-(2-amino-6-oxo-1,6-dihydropurin-7-yl)acetic acid. In some alternatives, the CAR or T cell receptor comprises a fragment specific for the hapten, wherein the CAR or TCR comprises 14G8, Anti 3-methylindole antibodies, 3F12, Anti 3-methylindole antibodies, 4A1G, Anti 3-methylindole antibodies, 8F2, Anti 3-methylindole antibodies, 8H1, Anti 3-methylindole antibodies, Anit-Fumonisin B1 antibodies, Anti-1,2-Naphthoquinone-antibodies, Anti- 15-Acetyldeoxynivalenol antibodies, Anti-(2-(2,4-dichlorophenyl)-3(1H-1,2,4-triazol-1-yl)propanol) Antibodies (Anti-DTP antibodies), Anti-22-oxacalcitriol antibodies (As-1, 2 and 3), Anti-(24,25(OH)2D3) Antibodies (Ab11), Anti-(24,25(OH)2D3) Antibodies (Ab3), Anti-(24,25(OH)2D3) Antibodies (Ab3-4), Anti-2,4,5-Trichlorophenoxyacetic acid antibodies, Anti (2,4,5-Trichlorphenoxyacetic acid) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti-(2,4,6-Trichlorophenol) Antibodies, Anti 2,4,6-Trinitrotoluene(TNT) Antibodies, Anti-2,4-Dichlorophenoxyacetic acid( MAb’s B5/C3, E2/B5, E2/G2, F6/C10, and F6/E5), Anti (2,4-Dichlorphenoxyacetic acid) Antibodies, Anti-2-hydroxybiphenyl-antibodies, Anti-(3,5,6-trichloro-2-pyridinol) Antibodies (LIB-MC2, LIB-MC3), Anti (3,5,6-trichloro-2-pyridinol) antibodies (LIB-MC2 MAb), Anti-3-Acetyldeoxynivalenol(3-AcDON) Antibodies, Anti-3-phenoxybenzoic acid (3-PBAc)-Antibodies, Anti -4-Nitrophenol antibodies, anti-4-nitrophenyl 4′-carboxymethylphenyl phosphate antibodies, Anti-7-(Carboxyethyl)guanine(7-CEGua) antibodies (group specific for 7-meGua), Anti-7-methylguanine(7-MEGua) antibodies, Anti-ABA antibodies, Anti Acephate antibodies (Antiserum 8377), Anti-acetyllysine antibodies (mAbs AL3D5, AL11, AKL3H6, AKL5C1), Anti Aculaetiside-A antibody, Anti Aflatoxin M1(AFM1)antibodies (mAbs A1, N12, R16, FF32), Anti-agatharesinol Antibody, Anti-agatharesinol Antibody, Anti Amidochlorantibodies, Anti-Amitrole antibodies (anti 1a-BSA antibodies), Anti ampicillin Antibodies( AMPI I 1D1 and AMPI II 3B5 ), Anti-anandamide antibodies (9C11.C9C, 30G8.E6C, 7D2.E2b, 13C2 MAbs), Anti atrazine antibodies, Anti-atrazine antibodies, Anti-Atrazine antibodies, Anti Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies, Anti-Atrazine Antibodies (4063-21-1 MAb cell line mAb and scAbs ), Anti-Atrazine Antibodies (4D8 and 6C8 scAb), Anti Atrazine Antibodies ( C193 ), Anti Atrazine Antibodies (In Rabbit/Sheep), Anti Atrazine Antibodies (K4E7), Anti Atrazine Antibodies ( MAb: AM7B2.1), Anti Atrazine Antibodies( ScAb), Anti Atrazine Mercapturic acid antibodies, Anti (Azinphos methyl) Antibodies (MAB’s LIB-MFH14, LIB-MFH110 ), Anti benalaxyl antibody, Anti benzimidazolecarboxylic acid, Anti benzimidazoles antibody (Ab 587), Anti-Benzo[a]pyrene antibodies, Anti Benzo(a)pyrene antibodies (10C10 and 4D5 MAbs), Anti-(Benzoylphenylurea)-Antibodies (mainly against Diflubenzuron), Anti-berberine Antibodies, Anti-beta Indole Acetic Acid Antibodies, Anti-Biopterin(L-erythro form) Antibodies, Anti-Brevetoxin PbTx-3-Antibodies, Anti Bromacil Antibodies, Anti-Bromophos Antibodies, Anti-Bromophos ethyl Antibodies, Anti Butachlor antibodies, Anti-Captopril-MCC Antibodies, Anti-Carbamazepine(CBZ)- Antibodies, Anti Carbaryl Antibodies, Anti Carbaryl Antibodies (LIB-CNH32, LIB-CNH33,LIB-CNH36, LIB-CNH37, LIB-CNH45, LIB-CNA38), Anti-Carbaryl Antibodies (LIB/CNH-3.6 MAb), Anti Carbofuran Antibodies(LIB-BFNB-52, LIB-BFNB-62, LIB-BFNB-67), Anti Carbofuran Antibodies(LIB-BFNP21), Anti-CDA-antibodies, Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]butanoic Acid ), Anti-CDA-antibodies (anti-2-[2-Chloro-(2′-6′-diethyl)acetanilido]ethanoic Acid), Anti-CDA-antibodies (anti- 5-(4-Chloroacetamido-3,5-diethyl)phenoxypentanoic Acid ), anti-ceftazidime antibody, Anti-(chlorodiamino-s-triazine)Antibodies (Anti-CAAT) (PAb1-8), Anti Chlorothalonil Antibodies, Anti-Chlorpyrifos antibodies, Anti-Chlorpyrifos Antibodies, Anti-Chlorpyrifos Antibodies(LIB-AR1.1, LIB-AR1.4 Mabs), Anti-Chlorpyrifos Antibodies (LIB-C4), Anti (chlorpyrifos) antibodies (LIB-C4 MAb), Anti-Chlorpyrifos Antibodies(LIB-PN1 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PN2 Mabs), Anti-Chlorpyrifos Antibodies(LIB-PO Mabs), Anti-chlorsulfuron antibodies, Anti-Chlorsulfuron antibodies, Anti Chlortoluron Antibodies (Antiserum), Anti-Cyanoginosin-LA antibodies (mAbs 2B2-2, 2B2-7, 2B2-8, 2B2-9, 2B2-10, 2B5-5, 2B5-8, 2B5-14, 2B5-15, 2B5-23), Anti(D-3-methoxy-4-hydroxyphenylglycol) antibodies, Anti-DDA antibodies, Anti DDT antibodies (PAbs and MAbs), Anti-DDT Mabs (LIB1-11, LIB5-21, LIB5-25, LIB5-28, LIB5-212, LIB5-51, LIB5-52, LIB5-53), Anti-DEC Antibodies (Anti diethylcarbamazine Antibodies), Anti DEHA antibodies, Anti-(Delor 103) antibodies, Anti-Deltamethrin Antibodies, Anti Deltamethrin Antibodies (Del 01 to Del 12 MAbs and PAbs), Anti-deoxynivalenol(DON) Antibodies, Anti-Deoxynivalenol(DON) Antibodies, Anti Dexamethasone Antibody, Anti Dexamethasone Antibody, Anti-Dinitrophenyl(DNP)-antibodies, Anti dinitrophenyl spin labeled antibodies (AN01 - AN12), Anti Diuron Antoboides (MAb’s : 21, 60, 195, 202, 275, 481, 488, 520), Anti -D-MHPG Antibodies, Anti DNC antibodies, Anti-EB1089 antibodies, Anti-ecdysone antibodies, Anti-endosulfan antibodies, Anti-Endosulfan antibodies, Anti Esfenvalerate antibodies (Ab7588), Anti estradiol antibodies, Anti-Fenitrothion antibodies (pAbs and mAbs), Anti-Fenpropimorph antibodies, Anti Fenthion Antibodies, Anti-Fenthion Antibodies, Anti FITC antobodies (B13-DEI), Anti-Flucofuron antibodies(F2A8/1/A4B3), Anti-flufenoxuron antibodies, and Anti-(Benzoylphenylurea)-Antibodies, Anti-Formononetin Antibodies, Anti-Furosemide antibodies (Furo-26, Furo37, furo-72, Furo 73 Mabs), Anti-GR151004 Antibodies, Anti-hCG-alpha-peptide Antibodies (FA36, Anti hydroxyatrazine antibodies (HYB-283-2), Anti-Hydroxysimazine Antibodies, Anti Imazalil Antibodies MoAb’s(9C1-1-1, 9C5-1-1, 9C6-1-1, 9C8-1-1, 9C9-1-1, 9C12-1-1, 9C14-1-1, 9C16-1-1, 9C18-1-1, 9C19-1-1, 9E1-1, 9G2-1), Anti Irgarol Antibodies, Anti Isopentenyl adenosine antibodies, Anti Isoproturon Antibodies, Anti-KB-6806 antiserum, Anti -(+)lupanine antibodies, Anti Lysophosphatidic(LPA) acid, Anti M3G Ab1 and Ab2, Anti M3G Ab1 and Ab2, Anti-MBC antibodies (Anti-2-succinamidobenzimidazole antiserum), Anti Metanephrine antibodies, anti (+)methamphetamine antibodies, Anti- Methiocarb Antibodies (LIB-MXNB31, LIB-MXNB-33, LIB-MXNH14 and LIB-MXNH-15 MAbs), Anti Metolachlor antibodies, Anti-Metolachlor Antibodies, Anti-Metolachlor Antibodies (MAb 4082-25-4), Anti Molinate Antibodies, Anti monuron antibodies, Anti-morphine-3-glucuronide(E3 scFv antibody), Anti morphine antibodies, Anti-Morphine antibodies, Anti-Morphine Antibodies (mAbs 8.2.1, 33.2.9, 35.4.12, 39.3.9, 44.4.1, 76.7F.16, 83.3.10, 115.1.3, 124.2.2, 131.5.13, 158.1.3, 180.2.4), Anti-Neopterin(D-erythro form) Antibodies, Anti-Nicarbazin Antibodies (Nic 6, Nic 7, Nic 8, and Nic 9), Anti Nicergoline Antibodies(Nic-1, Nic-2, Nic-3 & BNA-1, BNA-3), Anti-norflurazon antibodies, Anti NorMetanephrine antibodies, Anti (o-DNCP) Antibodies, Anti - P10 antibodies (TRH elongated peptide), Anti- Paraoxon Antibodies (BD1 and CE3), Anti Paraquat antibodies, Anti-Paraquat antibodies, anti Parathion-methyl antibodies, Anti PCB Antibodies (against 3,3’,4,4′-tetrachlorobiphenyl) MAb S2B1, Anti pentachlorophenol antibodies, Anti Pentachlorophenol antibodies, Anti-Pentachlorophenol antibodies, Anti permethrin antibodies (Mabs Py-1, Py-3 and Py-4), Anti- Phencyclidine Antibodies ( Mab 6B5 Fab ), Anti-phenobarbital antibodies, Anti-phenobarbital antibodies, Anti-(p.p′-DDT)- Antibodies (LIB-DDT-35 and LIB-DDT5-52), Anti permethrin antibodies(Ab549), Anti Propoxur antibodies (LIB-PRNP15, LIB-PRNP21, LIB-PRNB21, LIB-PRNB33), Anti-Prostaglandin E2-antibodies, Anti-p-tyramine antibodies, Anti pyrene antibodies, Anti retronecine antibodies, Anti-Retronecine Antibodies, Anti salicylate antibodies, Anti Sennoside A antibodies(MAb 6G8), Anti Sennoside B antibodies(MAb’s: 7H12, 5G6, 5C7), Anti Simizine antibodies, Anti Sulfonamides antibodies (Anti-TS), Anti-Sulocfuron antibodies(S2B5/1/C3), Anti sulphamethazine antibodies (21C7), Anti-synephrine antibodies, Anti-Thiabendazole antibodies (Antibody 300), Anti-Thiabendazole antibodies (Antibody 430 and 448), Anti-Thiram-Antibodies, Anti- THP antibodies (7S and 19S ), Anti- Thromboxane B2 Antibodies, Anti-thymidine glycol monophosphate antibodies (mAb 2.6F.6B.6C), Anti - Thyroliberin (TRH) antibodies, Anti TNT antibodies(AB1 and AB2 antiserum), Anti Triadimefon Antibodies, Anti-triazine antibodies ( AM1B5.1), Anti-triazine antibodies ( AM5C5.3), Anti-triazine antibodies ( AM5D1.2), Anti-triazine antibodies ( AM7B2.1), Anti-triazine antibodies ( SA5A1.1), Anti-Triazine serum (anti-ametryne), Anti-Triazine serum (anti-atrazine), Anti-Triazine serum (anti-simazine), Anti-Triazine serum (anti-simetryne), Anti Trifluralin Antibodies, Anti Trifluralin Antibodies, Anti Vincristine Antibodies, Anti-Zearalenone Antibodies, Anti Zeatin riboside antibodies, E2 G2 and E4 C2, Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), LIB-BFNP23 Mab, MAb’s H-7 and H-9 (against O,O-diethyl OP pesticides), MoAb 33A7-1-1, MoAb 33B8-1-1, MoAb 33C3-1-1, MoAb 3C10-1-1 and MoAb 3E17-1-1, MoAb 45D6-5-1, MoAb 45E6-1-1, MoAb 45-1-1, Mutant (GlnL89Glu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (G1nL89Glu/ ValH37Ile/GluL3Val)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile/GluL3Val) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (G1nL89Glu/ ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlnL89Glu/ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50Gln) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GluH50X) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aAla) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (GlyH100aSer) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (HisH95Tyr) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (PheL32Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TrpH33Phe,Tyr,Leu) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (Try196Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (TryL96Phe) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile) in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), Mutant (ValH37Ile)in Fab Fragment K411B derived from MAb K4E7 (isotype IgG2b with k light chain), P6A7 MAb, PNAS2 6/3 56(1)-1 -5 -1, PNAS2 6/3 56(1)-1 -5 -2, PNAS2 6/3 56(1)-1 -10 -4, PNAS2 6/3 56(1)-1 -10 -5 and PNAS2 6/3 56(1)-3 -1 -5, Alexa Fluor 405/Cascade Blue dye antibody, Alexa Fluor 488 dye antibody, BODIPY FL dye antibody, Dansyl antibody, Fluorescein/Oregon Green dye antibody, Lucifer yellow dye antibody, Tetramethylrhodamine and Rhodamine Red dye antibody, Texas Red and Texas Red-X dye antibody, Biotin antibody, Dinitrophenyl antibody and/or Nitrotyrosine antibody or any portion thereof of the aforementioned haptens.
- In some alternatives, herein, the cells provided are cytotoxic T lymphocytes. “Cytotoxic T lymphocyte” (CTL) has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a T lymphocyte that expresses CD8 on the surface thereof (e.g., a CD8+ T cell). In some alternatives such cells are preferably “memory” T cells (TM cells) that are antigen-experienced. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells.
- “Masking moiety” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a moiety on the lipid ether that is bound to the target moiety. The masking moiety functions as a protective group to prevent recognition of the lipid’s target moiety by blocking binding and recognition of a chimeric antigen receptor that is specific for the target moiety. When the lipid is integrated into a cell, wherein the cell exists in a tumor environment or site of reactive oxygen species, the masking moiety can be self-cleaved, thus allowing binding and recognition of the target moiety by the chimeric antigen receptor. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the phospholipid ether comprises a target moiety and the CAR is joined to said phospholipid ether through an interaction with said target moiety. In some alternatives, the phospholipid ether comprises a polar-head group and a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the masking moiety is removed when the composition is within an acidic environment. In some alternatives, the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values. In some alternatives, the masking moiety is removed by nitrosylation.
- “Cancer,” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Subjects that can be addressed using the methods described herein include subjects identified or selected as having cancer, including but not limited to colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, and brain cancer, etc. Such identification and/or selection can be made by clinical or diagnostic evaluation. In some alternatives, the tumor associated antigens or molecules are known, such as melanoma, breast cancer, brain cancer, squamous cell carcinoma, colon cancer, leukemia, myeloma, and/or prostate cancer. Examples include but are not limited to B cell lymphoma, breast cancer, brain cancer, prostate cancer, and/or leukemia. In some alternatives, one or more oncogenic polypeptides are associated with kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia. In some alternatives, a method of treating, ameliorating, or inhibiting a cancer in a subject is provided. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer. In some alternatives, the subject is selected to receive an additional cancer therapy, which can include a cancer therapeutic, radiation, chemotherapy, or a drug for the treatment of cancer. In some alternatives, the drugs comprise Abiraterone, Alemtuzumab, Anastrozole, Aprepitant, Arsenic trioxide, Atezolizumab, Azacitidine, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Carboplatin, Cetuximab, Chemotherapy drug combinations, Cisplatin, Crizotinib, Cyclophosphamide, Cytarabine,Denosumab, Docetaxel, Doxorubicin, Eribulin, Erlotinib, Etoposide, Everolimus, Exemestane, Filgrastim, Fluorouracil, Fulvestrant, Gemcitabine, Imatinib, Imiquimod, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Letrozole, Leuprolide, Mesna, Methotrexate, Nivolumab, Oxaliplatin, Paclitaxel, Palonosetron, Pembrolizumab, Pemetrexed, Prednisone, Radium-223, Rituximab, Sipuleucel-T, Sorafenib, Sunitinib, Talc Intrapleural, Tamoxifen, Temozolomide, Temsirolimus, Thalidomide, Trastuzumab, Vinorelbine or Zoledronic acid.
- “Tumor microenvironment” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a cellular environment, wherein a tumor exists. Without being limiting, the tumor microenvironment can include surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules and/or the extracellular matrix (ECM).
- Described herein are synthetic molecular structures that are designed to decorate or label cancer cell membranes, such as tumor cell membranes. These synthetic structures contain recognition moieties that interact specifically with CAR T cells that are designed to target these recognition moieties. The molecular domains of phospholipid ether (PLE) CAR T cell tumor targeting (PLE-CTCT’s) agents comprise a cell membrane integrating domain composed of a lipid housing a polar-head group. In some alternatives, the lipid is a phospholipid ether. Without being limiting, the polar-head group can comprise of a phosphocholine and the carbon alkyl chain can comprise a preferred length of 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons, preferably 18 carbons. The lipid (PLE) when administered may also target tumor and cancer cells. The lipid (PLE) may be administered intravaneously. From this PLE backbone, an extracellular extension from the polar-head group is conceived to be composed of a spacer and a molecular structure to which a CAR binds to at affinities that induce a CAR-expressing effector cell, preferably a T cell, activation signaling. Further, the CAR recognition moiety of the PLE-CTCT is chemically modified such that the target moiety is masked from CAR recognition until it is chemically modified or unmasked by the tumor cell, tumor microenvironment (e.g., proteases present in the tumor microenvironment) or the tumor’s milieu. In one exemplary alternative, the target moiety is fluorescein and the masking modification comprising a phenolic hydroxy group, is introduced to a hydroxyl on the xanthene moiety of the fluorescein molecule. In this alternative, the masking modification is removed from the fluorescein in a reactive oxygen species (ROS) reaction, which can occur in a tumor microenvironment. In general, masking elements are conceived that become unmasked by hydrolysis that is dependent on ROS, low pH, hypoxia, nitrosylation, protease digestion, and other chemical reactions taking place in the tumor microenvironment. In some alternatives herein, the unmasking is due to hydrolysis that is dependent on ROS, low pH, hypoxia, or nitrosylation within a tumor microenvironment.
- As described in the alternatives herein, human tumor therapy is conceived in which patients receive infusions of PLE-CTCT’s in combination with infusions of PLE-CTCT specific CAR T cells. The PLE-CTCT, when administered, may also target tumor and cancer cells. Administration may be by intravenous administration. In this exemplary alternative, this system represents a universal target antigen used in combination with a universal CAR and/or universal CAR expressing anti-tumor effector cell. In order to demonstrate proof-of-concept for this PLE-CTCT system, a PLE (18C alkyl chain) having a fluorescein (FL) appended CAR recognition element appended to the polar-head group’s choline via PEG spacers was synthesized for use in the alternatives described herein. It was demonstrated that FL-specific scFv CAR T cells exhibit a redirected antitumor function in vitro and in vivo to tumors loaded with FL PLE-CTCT’s. Moreover, a FL PLE-CTCT housing a ROS responsive mask, is described in an exemplary alternative herein for further specification of targeting agent to tumor cells with active ROS microenvironments.
- Autologous T cells can be genetically modified to express transgenes that are engineered to enhance efficacy after transfer in vivo. Despite successful adoptive transfer of transgene modified T cells in the setting of CD19 B cell lineage malignancies, no universal CAR target antigen that is present on all forms of cancer but not normal cells has been identified. Thus, the field is hampered by the need to identify cell surface targets that are naturally present on tumor cells and minimally expressed by normal cells/tissues of the body. Thus, CAR T cell therapeutic development is hampered by the prospect of potentially needing tens to hundreds of vetted CAR targets and CARs to cover the majority of cancer types afflicting humans.
- The conception of PLE-CTCT’s is that a synthetic exogenously delivered molecular construct that A) integrates into all cellular membranes of cancer cells (e.g., tumor cells) but is selectively rapidly catabolized by normal cells relative to tumor cells, and B) is equipped with masking elements that selectively “unmask” on tumor cells, provides for a “universal target” for CAR T cell immunotherapy, wherein the CAR is specific to the unmasked target moiety of the PLE-CTCT.
- The PLE’s as described herein, have the capacity for differential slow tumor membrane clearance compared to normal cell rapid clearance. These PLE’s have been conceived to carry imaging and radiotherapeutic payloads by modification to the alkyl chain of the PLE, which is buried within the lipid bilayers. As described in some alternatives herein, the target moieties were chemically built out from the PLE’s polar-head group to present the target moieties to CAR effector cells that would necessarily have to occur on the extracellular side of the tumor cell’s plasma membrane.
- There are a number of different approaches to cancer therapy. This can include surgery, targeted drug delivery, chemotherapy and radiation. However, these approaches have only limited effectiveness. For example, although radiation therapy is a tool often used to treat cancer in an attempt to improve local tumor control, a key challenge is the limitation of dose escalation due to toxicity of neighboring sensitive normal organs. Additionally, one critical problem with many cancer treatments is that despite initial responses, cancers become resistant to conventional therapies, and the cells that persist after treatment drive disease relapse. As such, the methods provided herein can be used with and without these additional anti-cancer therapies so as to specifically target drug resistant residual disease or cancers.
- Examples of lipid CAR T cell tumor targeting agents are shown in
FIGS. 1A and 1B . As shown are the structure of FL-PLE (1A) and ProFL-PLE (1B). (i) FL (fluorescein), the target for CAR T cells. (ii) Polyetheneglycol (PEG), the spacer used to extend the target an ideal distance from the cell surface. (iii & iv) PLE, iii is the polar head group and iv is the hydrophobic tail for incorporation or tethering into the cell plasma membrane. (v) Masking moiety, to prevent anti-FLCAR T cell recognition. (vi) The cleavage point where ProFL-PLE is unmasked. Unmasking to occur once or just before anti-FLCAR T-cells are in the reactive oxygen species (ROS) rich environment afforded by the tumor. This will in turn create the FL-PLE. - The lipid CAR T cell tumor targeting (CTCT) agents integrate into the membrane as shown in
FIG. 2 . The CTCT agent is preferential for a tumor cell, or a tumor cell membrane. The CTCT agent can embed into a lipid raft on the cell membrane of a tumor cell and the masking moiety can be removed inside a ROS rich tumor microenvironment so that recognition and interaction with the specific CAR T cells can take place. - Described herein are complexes that comprise a chimeric antigen receptor (CAR) or TCR joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid is a phospholipid ether. In the alternatives herein, the lipid may target a tumor or a cancer cell or tumor or cancer cell membrane. The chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety. In some alternatives, the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the PLE) and the transmembrane domain of the chimeric receptor. In some alternatives, the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths. In some alternatives, a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids. In some alternatives, the spacer is optimized or selected to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety. In some alternatives, the CAR comprises a co-stimulatory domain. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises at least 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid further comprises a spacer that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment.
- In some alternatives, the complex comprises a chimeric antigen receptor (CAR) joined to an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a target moiety and the CAR is joined to said antibody or fragment thereof through an interaction with said target moiety.
- Described herein are complexes that comprise a chimeric antigen receptor (CAR) or TCR joined to a targeting peptide, wherein the targeting peptide targets a tumor cell or a cancer cell, wherein the targeting peptide comprises a target moiety and the CAR is joined to said peptide through an interaction with said target moiety. The chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety. In some alternatives, the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the targeting peptide and the transmembrane domain of the chimeric receptor. In some alternatives, the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths. In some alternatives, a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids. In some alternatives, the spacer is optimized or selected to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety. In some alternatives, the CAR comprises a co-stimulatory domain. In some alternatives, the targeting peptide comprises hydrophobic amino acids for integrating into the membrane of the target cell (e.g., a tumor cell or cancer cell). In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the targeting peptide further comprises a spacer that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a poly(carboxybetaine), a peptide spacer, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the targeting peptide is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment.
- In some alternatives, the complex comprises a chimeric antigen receptor (CAR) joined to an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a target moiety and the CAR is joined to said antibody or fragment thereof through an interaction with said target moiety.
- Described herein are cells comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) bound to a lipid, wherein the lipid comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety. In some alternatives, the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the PLE) and the transmembrane domain of the chimeric receptor. In some alternatives, the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths. In some alternatives, a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids. In some alternatives, the spacer is optimized to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety. In some alternatives, the CAR comprises a co-stimulatory domain. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid further comprises a spacer group that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment.
- Also described herein are cells comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) bound to an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the antibody or fragment thereof.
- Described herein are cells comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) bound to a targeting peptide, wherein the targeting peptide targets a tumor or cancer cell, wherein the targeting peptide comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid. In some alternatives, the chimeric antigen receptor can comprise an antibody, antibody fragment, ScFv or other binding moiety that is specific for the target moiety. In some alternatives, the chimeric antigen receptor further comprises a spacer region found between the ligand binding domain (the site that recognizes the target moiety on the PLE) and the transmembrane domain of the chimeric receptor. In some alternatives, the spacer region has at least 10 to 229 amino acids, 10 to 200 amino acids, 10 to 175 amino acids, 10 to 150 amino acids, 10 to 125 amino acids, 10 to 100 amino acids, 10 to 75 amino acids, 10 to 50 amino acids, 10 to 40 amino acids, 10 to 30 amino acids, 10 to 20 amino acids, or 10 to 15 amino acids, or a length within a range defined by any two of the aforementioned lengths. In some alternatives, a spacer region has 12 amino acids or less, 119 amino acids or less, or 229 amino acids or less but greater than 1 or 2 amino acids. In some alternatives, the spacer is optimized to increase the flexibility of the chimeric antigen receptor in order to allow binding to the target moiety. In some alternatives, the CAR comprises a co-stimulatory domain. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, targeting peptide comprises hydrophobic amino acids. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the targeting peptide further comprises a spacer group that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell exists in a tumor microenvironment.
- Also described herein are cells comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) bound to an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the antibody or fragment thereof.
- A method of treating, ameliorating, or inhibiting a cancer in a subject is described herein. The method comprises a) introducing, providing, or administering to a subject a composition that comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor, which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to and/or interact with the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying a subject in need of a therapy for cancer prior to steps a-c. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. Administration of the composition and the CAR T cell may be by intravenous administration. In some alternatives, the hydrophobic group comprises a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the cell is provided to the subject the cell is provided to the
subject subject - In some embodiments is provided a method comprising a) introducing, providing, or administering to a subject a composition that comprises an antibody or binding fragment thereof, which comprises a target moiety, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR), such as a T cell, which is specific for the target moiety, and, c) optionally, measuring or evaluating the binding of the cell comprising the CAR to the antibody or fragment thereof, after steps a-c and/or d) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-b, and/or e) optionally, identifying a subject in need of a therapy for cancer prior to steps a-b. In some embodiments, the antibody or binding fragment thereof comprising a target moiety is an antibody or binding fragment thereof specific to a cancer cell or a pathogenic cell. In some embodiments, the antibody or binding fragment thereof comprising the target moiety is specific to a tumor cell. Administration of the composition and the CAR T cell may be by intravenous administration. In some embodiments, the antibody or binding fragment thereof comprising the target moiety includes abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, or zatuximab, or a derivative, analogue, or binding fragment thereof.
- In some embodiments, the antibody or binding fragment thereof, which comprises the target moiety, includes cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, or umavizumab or a derivative, analogue, or binding fragment thereof. In some embodiments, the antibody or binding fragment thereof includes, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a derivative, analogue, or binding fragment thereof. In some embodiments, the antibody or binding fragment thereof includes actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- A method of treating, ameliorating, or inhibiting a cancer in a subject is described herein. The method comprises a) introducing, providing, or administering to a subject a composition that comprises a targeting peptide, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor, which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to and/or interact with the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the targeting peptide, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying a subject in need of a therapy for cancer prior to steps a-c. In some alternatives, targeting peptide comprises hydrophobic amino acids. IIn some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. In some alternatives, the targeting peptide comprises a spacer for the targeting moiety. In some alternatives, the spacer comprises a poly(carboxybetaine), peptide, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the cell is provided to the subject the cell is provided to the
subject subject - In some embodiments is provided a method comprising a) introducing, providing, or administering to a subject a composition that comprises an antibody or binding fragment thereof, which comprises a target moiety, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR), such as a T cell, which is specific for the target moiety, and, c) optionally, measuring or evaluating the binding of the cell comprising the CAR to the antibody or fragment thereof, after steps a-c and/or d) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-b, and/or e) optionally, identifying a subject in need of a therapy for cancer prior to steps a-b. In some embodiments, the antibody or binding fragment thereof comprising a target moiety is an antibody or binding fragment thereof specific to a cancer cell or a pathogenic cell. In some embodiments, the antibody or binding fragment thereof comprising the target moiety is specific to a tumor cell. In some embodiments, the antibody or binding fragment thereof comprising the target moiety includes abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, or zatuximab, or a derivative, analogue, or binding fragment thereof. Administration of the composition and the CAR T cell may be by intravenous administration.
- In some embodiments, the antibody or binding fragment thereof, which comprises the target moiety, includes cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, or umavizumab or a derivative, analogue, or binding fragment thereof. In some embodiments, the antibody or binding fragment thereof includes, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a derivative, analogue, or binding fragment thereof. In some embodiments, the antibody or binding fragment thereof includes actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- In some alternatives herein, the binding site of the chimeric antigen receptor (CAR) is designed so as to bind and/or interact with a target moiety of the FL-PLE. The targeting moiety may be a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. The CAR comprises an antibody or antibody fragment, ScFv or a protein or portion thereof that is designed to recognize the target moiety. Designing proteins for interactions are known to those skilled in the art, and are desirably very specific, as proteins can interact with a large number of proteins or chemicals such as FL, for example, thus successful design should utilize selective binders. Thus, protein design algorithms can be used to distinguish between on target and off target binding. The protein can also be designed by focusing on electrostatic contributions, so as to increase the affinity for its binding partner, or target moiety. Screening of a variety of different CAR structures can be performed by contacting cells comprising CARs, which are specific for a target moiety, with a substrate or binding agent comprising said target moiety and evaluating the binding of the CARs to said substrate or binding agent. Additionally, a target cell or a target virus unto which the binding agent is specific can be added so that the formation of a complex comprising the cell, which comprises the CAR, bound to the binding agent by virtue of the interaction of the CAR and the target moiety, and a target cell or virus unto which the binding agent is specific for can be evaluated. In some alternatives, the scFv is specific for the FL-PLE. However, increasing the binding affinity of a CAR does not always increase the effects that one would expect for a high affinity binding CAR.
- In some alternatives herein, the binding site of the chimeric antigen receptor (CAR) is designed so as to bind and/or interact with a target moiety of the targeting peptide. The targeting moiety may be a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. The CAR comprises an antibody or antibody fragment, ScFv or a protein or portion thereof that is designed to recognize the target moiety. Designing proteins for interactions are known to those skilled in the art, and are desirably very specific, as proteins can interact with a large number of proteins or chemicals such as FL, for example, thus successful design should utilize selective binders. Thus, protein design algorithms can be used to distinguish between on target and off target binding. The protein can also be designed by focusing on electrostatic contributions, so as to increase the affinity for its binding partner, or target moiety. Screening of a variety of different CAR structures can be performed by contacting cells comprising CARs, which are specific for a target moiety, with a substrate or binding agent comprising said target moiety and evaluating the binding of the CARs to said substrate or binding agent. Additionally, a target cell or a target virus unto which the binding agent is specific can be added so that the formation of a complex comprising the cell, which comprises the CAR, bound to the binding agent by virtue of the interaction of the CAR and the target moiety, and a target cell or virus unto which the binding agent is specific for can be evaluated. In some alternatives, the scFv is specific for the FL-PLE. However, increasing the binding affinity of a CAR does not always increase the effects that one would expect for a high affinity binding CAR.
- Also described herein, are the methods of treatment, inhibition, or amelioration of cancer in mouse models of cancer. Mice that can be used for these evaluations include mice with mutations in the MSH2 and/or MLH1 genes. These mice are susceptible to developing gastrointestinal cancer and tumors that are classified as adenomas, invasive adenocarcinomas and late stage carcinomas.
- In order to test for the efficacy of the compositions and CAR T cells expressing CARs that are specific for the target moiety, several groups of mice are selected for the study: 1) Control mice; 2) Mice given the FL-PLE; 3) Mice given the CAR T cell; 4) Mice given the FL-PLE followed by the
CAR T cell 1 hour after FL-PLE administration; 5) Mice given the FL-PLE followed by theCAR T cell 2 hours after FL-PLE administration; 6) Mice given the FL-PLE followed by theCAR T cell 4 hours after FL-PLE administration; 7) Mice given the FL-PLE followed by theCAR T cell 6 hours after FL-PLE administration; 8) Mice given the FL-PLE followed by the CAR T cell 12 hours after FL-PLE administration; 9) Mice given the FL-PLE followed by the CAR T cell 24 hours after FL-PLE administration; and 10) Mice given the FL-PLE followed by the CAR T cell 48 hours after FL-PLE administration. Administration of the composition and the CAR T cell may be by intravenous administration. Each group of the mice have mutations in the MSH2 and MLH1 genes and have early stage tumors as detected by diffusion weighted whole body imaging. Each group of mice have 5 males and 5 females aged 16 weeks. Experiments were also performed where tumors are engrafted atday 0 and days 5-7. FL-PLEs are injected for integration into cells and this is followed by T cells injected onday 7. FL-PLE’s may then be redosed weekly or bi weekly. - Three weeks after the administration of the drugs, the tumors are again analyzed for size by diffusion weighted whole body imaging to review the sizes of the tumors in the mice. It is expected that the mice that were administered the FL-PLE followed by the CAR T cell will have an appreciable reduction and/or inhibition of tumor growth.
- Shown in
FIG. 3 is the synthesis of a FL-PLE. The synthesized FL-PLE was subjected to an NMR analysis. A 1D NMR spectra was obtained with the FL-PLE sample in a buffer solution (FIG. 4 ). As shown, the 1D spectra of the sample of the synthesized FL-PLE indicated peaks for the specific groups on the molecule which were expected for the synthesized structure of the FL-PLE. - Shown in
FIG. 5 , is the synthesis scheme for ProFL-PLE. A 1D NMR spectra was obtained with the ProFL-PLE sample in a buffer solution (FIG. 6 ). As shown, the 1D spectra of the sample of the synthesized ProFL-PLE indicated peaks for the specific groups on the molecule which were expected for the synthesized structure of the ProFL-PLE. - Cells were incubated with 5 µM (unless otherwise stated) FL-PLE overnight then cells were analyzed by flow or confocal microscope. The level of FL-PLE integration into the cell membrane was identified by the signal intensity emitted from the fluorescein moiety of the FL-PLE.
FIG. 7A shows FL-PLE is able to integrate into multiple cancers: Be2 (neuroblastoma), U87 (glioblastoma), and daoy (medulloblastoma). InFIGS. 7B, U87 cells were incubated overnight in the presence of 0, 0.1, 1, or 5 µM FL-PLE and then subjected to flow analysis. The results demonstrate that FL-PLE integration into the cancer cell membrane is concentration dependent. InFIGS. 7C, U87 cells were incubated overnight in the presence of 5 µM FL-PLE, washed to remove residual FL-PLE, cultured in fresh (FL-PLE free) media for up to 4 days, and then subjected to flow analysis. Results demonstrate a multiday FL-PLE retention time. InFIG. 7D , confocal images show that FL-PLE integrates over the whole cell surface (U87 cells). The FL-PLE is shown in green and the nucleus is stained with DAPI, which is shown in blue. InFIG. 7E , after a glioblastoma (U87 cells) tumor was established in a group of mice by intracranial injection, the mice received an intravenous injection of FL-PLE. Mice were sacrificed and brains were harvested at various time points post FL-PLE injection. The fluorescent image of a brain harvested 2 days post FL-PLE injection demonstrates that FL-PLE preferentially targets and integrates into the tumor in an in vivo environment. - The use of the system led to the surprising effect of having the FL-PLE preferentially targeting the tumor and integrating into the cells that are within the tumor environment specifically.
- U87 cells were incubated with 5 mM FL-PLE overnight then imaged by confocal microscopy. Same as
FIG. 7D except this time U87 cells (nucleus shown in blue, DAPI) with FL-PLE (green) integrated into the membrane were stained with an antifluorescein antibody conjugated with an Alex 647 fluorophore (grey). These images demonstrate that the FL moiety is accessible for binding. InFIG. 8 , the use of the FL-PLE led to the surprising effect of having the FL-PLE integrate into the membrane demonstrating that it is accessible for CAR recognition, binding, and interaction. As shown, the lipids are able to target lipid rafts in cancer. - Cell integration of FL-PLE was analyzed by flow cytometry (
FIG. 9A ). There is a clear shift from the control K562 parental with the K562 parental incubated with 5 µM FL-PLE; whereas there is a very slight shift with K562 parental incubated with 0.5 µM FL-PLE. This slight shift corresponds to a difference in the amount of FL exposed on the surface of the cell for CAR T cell recognition. Also, the K562+OKT3 cells (a cell line created to test the endogenous activation of T cells through the TCR) match the K562 parental exactly, as expected. These cells were used in a chromium release assay (FIG. 9B ) and a cytokine release assay (FIG. 9C ) to test the activation of CD8+ antiFL CAR T cells compared with a CD8+ mock T cells. From these experiments, it was determined that antiFL CAR T cells recognize the FL moiety of the FL-PLE, which has integrated into the plasma membrane of target cells and activation occurred as a result of this binding and/or interaction event. The amount of the activation was dependent on the amount of FL exposed on the surface of the cell. - U87 cells harboring a green fluorescent protein and firefly luciferase fusion protein (GFP-ffLuc) were incubated with FL-PLE overnight. Note, the GFP-ffLuc allows for real-time monitoring of tumor progression via luminescent imaging. These cells were then mixed with CD8+ antiFL CAR T cells or CD8+ mock T cells at a 1:1 or 10:1 effector to target (E:T) ratio. Cell mixtures were injected into the brain of a mouse and tumor engraftment was monitored by luminescent flux over time. Here the antiFL CAR T cell was able to activate and slow down the engraftment of the tumor at a 10:1 (E:T). This demonstrates that the FL-PLE works as a target for CAR T-cell recognition in a living model. (
FIG. 10 ). - U87 cells were incubated with 5 µM ProFL-PLE overnight then imaged by confocal microscopy. The nucleus of the cells were stained with DAPI (blue). The same procedure as shown in
FIG. 5D was used. ProFL-PLE is not fluorescent due to the presence of the masking agent, a phenolic hydroxy group. When ProFL-PLE is introduced to a ROS environment, as modeled by the presence of H2O2, it is unmasked revealing the FL moiety. Therefore, the unmasked ProFL-PLE has the ability to emit green fluorescence (green). The image of ProFL-PLE integrated into the U87 cells shows almost no green fluorescence. Cells that were exposed to the ROS environment then emit green fluorescence, showing that ProFL-PLE was unmasked while being integrated into the cell membrane of the target cell. As shown, the use of the ProFL-PLE led to the surprising effect of having the ProFL-PLE integrate into the membrane of the target cell and evidence was found that this recognition moiety was accessible for CAR recognition, binding, and interaction. Also surprising was the unmasking of the lipid within a H2O2 rich environment for recognition by a CAR T cell providing evidence that the system would work in a tumor microenvironment. - Shown in
FIG. 12 is an example of a construction scheme for the synthesis of fluorescein-PEG-phosphatidylcholine. - Shown in
FIG. 13 is an example of a construction scheme for the synthesis of fluorescein-PEG. - Shown in
FIG. 14 is an example of a construction scheme for ProFL-NHS. - As described herein, there are many types of lipids that can be used for intercalating into the target cell. In some alternatives, the target cell is a cancer cell such as a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor comprises a plurality of cancer cells. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer. In some alternatives, the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide. In some alternatives, a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar head group and a hydrophobic moiety. In some alternatives, the hydrophobic moiety is a hydrophobic carbon tail. In some alternatives the hydrophobic carbon tail is saturated or unsaturated. In some alternatives, the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value. In some alternatives, the hydrophobic moiety is a steroid or a cholesterol or comprises an aromatic ring. In some alternatives, the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid contains branched alkyl tails. In some alternatives, the lipid can be a sphingolipid. The sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. In some alternatives, the lipid is a glycosphingolipid. As provided herein, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group comprises a fatty acid such as an aliphatic chain. The fatty acid can be saturated or unsaturated depending on the desired embodiments. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or comprises an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the lipid is a single chain alkylphospholipid. In some alternatives, the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine. In some alternatives, the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine. Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety). In some alternatives of the lipids described herein, a choline within the polar head group can be substituted with a piperidine moiety. In some alternatives, the lipid is an anticancer alkylphospholipid. Anticancer phospholipids are described e.g., in vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety).In some alternatives, the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein). Without being limiting the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and/or Erufosine. In some alternatives, the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine. In some alternatives, the lipid is a stable analog of lysophosphatidylcholine. In some alternatives, the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine. In some alternatives, the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine. In some alternatives herein, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the phospholipid ether comprises a polar-head group and a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group. In some alternatives the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the sugar is a glycerol. In some alternatives, the polar head group of the lipid comprises glycerol. In some alternatives, the polar head group of the lipid comprises a phosphate group. In some alternatives, the polar head group of the lipid comprises choline. In some alternatives, the lipid is a phosphatidylethanolomine. In some alternatives, the lipid is a phosphatidylinositol. In some alternatives, the lipid comprises a sphingoid base backbone. In some alternatives, the lipid comprises a sterol lipid, such as cholesterol or its derivatives. In some alternatives, the lipid comprises saccharolipids. In some alternatives, the polar head group comprises choline, phosphate and/or glycerol. In some alternatives, the lipid is a glycolipid. In some alternatives, the lipid comprise a sugar. In some alternatives, the lipid is derived from sphingosine. In some alternatives, the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR.
- The lipid can comprise a spacer that separates the target moiety from the lipid and is bound to the polar-head group of the lipid. The spacer of the lipid can comprise a poly(carboxybetaine), peptide, Polyglycidols, polyethylene, Polyanhydrides, Polyphosphoesters, Polycaprolactone, Poly(ethylene oxide), PEG spacer, a Hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the hapten spacer comprises two haptens and is referred to as a hapten (2X) spacer. In some alternatives, the lipid comprises a hydrophobic group such as an alkane chain. In some alternatives, the alkane chain can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons, or any number of carbons in between a range defined by any two aforementioned values. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the spacer comprises at least two haptens, at least three haptens or at least four haptens. In some alternatives, the FL-PLE comprises multiple fluoresceins. In some alternatives, the FL-PLE comprises 1, 2, 3, 4 or 5 flourescein moieties.
- As described herein, various antibodies or binding fragments thereof, which comprise a target moiety, may be used for recognizing a target cell. In some alternatives, a target cell is a cancer cell or a pathogenic cell. In some embodiments, the target cell is a tumor cell. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor comprises a plurality of cancer cells. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer. In some alternatives, the target cell is a virus or a bacteria. In some embodiments, the antibody is a full antibody or a binding fragment thereof that specifically binds to an antigen on a target cell. In some alternatives, the antigen is an angiopoietin, a transmembrane receptor, a cell adhesion molecule, a cluster of differentiation molecule, a ganglioside, a glycoprotein, a growth factor, an integrin, an interleukin, a Notch receptor, a transmembrane glycoprotein, a tumor necrosis factor, or a tyrosine kinase. In some embodiments, antigen is 5T4, B7-H3, carbonic anhydrase IX, carcinoembryonic antigen, CA-125, CD-3, CD-19, CD-20, CD-22, CD-30, CD-33, CD-38, CD-40, CD-51, CD-52, CD-56, CD-70, CD-74, CD-79b, CD-138, CD-221, CD-319, CD-326,
cell adhesion molecule 5, CTLA-4, cytokeratin polypeptides,death receptor 2, DLL4, EGFL7, EGFR, endosialin, EpCAM, FAP, FR-alpha, fibronectin, frizzled receptors, GD2, GPNMB, HER-1, HER-2, HER-3, IGF-IR, IGLF2, LOXL2, mesothelin, MS4A1, mucin 5AC, MUC1, Nectin-4, neuropilin, N-glycolyl GM3, PSMA, SLAMF7, TAG-72, TRAIL, TYRP1, VEGF, or other cancer expressing antigens. In some alternatives, the antibody or binding fragment, which is conjugated with a target moiety, thereof may bind specifically to a viral antigen or a bacterial antigen, including, for example by binding to an antigen of a Bacillus, a Candida, a Clostridium, a cytomegalovirus, an Ebola virus, an Escherichia, a Gram-negative bacteria, a Gram-positive bacteria, a hepatitis virus, a herpes virus, an HIV, an influenza virus, a Pseudomonas, a Staphylococcus, or a syncytial virus. For example, an antibody or fragment thereof may bind to a core antigen of HBV or HCV. - In some alternatives, a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to an antibody or binding fragment thereof, wherein the antibody or binding fragment thereof comprises a target moiety and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety. In some alternatives, the antibody or binding fragment thereof, which comprises a target moiety, comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, tefibazumab, actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- In some alternatives, the antibody or binding fragment thereof comprises a target moiety and the CAR is joined to said antibody or binding fragment thereof through an interaction with said target moiety. In some alternatives, the antibody or binding fragment thereof further comprises a target moiety, which interacts with the CAR or TCR.
- Some alternatives include a kit that comprises a pharmaceutical grade PLE-CTCT, which can be used with a CAR T cell product designed to be specific for a recognition moiety on said PLE-CEC in the tumor or cancer.
- Some alternatives include a kit that comprises an antibody or binding fragment thereof labeled with a target moiety, which can be used with a CAR T cell product designed to be specific for a recognition moiety on said labeled antibody or binding fragment thereof.
- In some alternatives, the antibody or binding fragment thereof, which comprises the target moiety, comprises abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, tefibazumab, actoxumab, bezlotoxumab, efungumab, obiltoxaximab, suvratoxumab, or urtoxazumab, or a derivative, analogue, or binding fragment thereof.
- In some alternatives, a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 18 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid further comprises a spacer that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x), (3x), (4x), or (5x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the CAR or TCR is expressed by a cell or a T cell. In some alternatives, the CAR or TCR is on the surface of a cell or a T cell. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor is from a cancer. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer. In some alternatives, the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide. In some alternatives, a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar head group and a hydrophobic moiety. In some alternatives, the hydrophobic moiety is a hydrophobic carbon tail. In some alternatives the hydrophobic carbon tail is saturated or unsaturated. In some alternatives, the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value. In some alternatives, the hydrophobic moiety is a steroid or a cholesterol. In some alternatives, the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid contains branched alkyl tails. In some alternatives, the lipid can be a sphingolipid. The sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. In some alternatives, the lipid is a glycosphingolipid. As provided herein, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group comprises a fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the lipid is a single chain alkylphospholipid. In some alternatives, the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine. In some alternatives, the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine. Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety). In some alternatives of the lipids described herein, a choline within the polar head group can be substituted with a piperidine moiety. In some alternatives, the lipid is an anticancer alkylphospholipid. Anticancer phospholipids are described by vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety). In some alternatives, the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein). Without being limiting the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and/or Erufosine. In some alternatives, the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine. In some alternatives, the lipid is a stable analog of lysophosphatidylcholine. In some alternatives, the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine. In some alternatives, the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine. In some alternatives herein, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar-head group and a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the lipid is a phospholipid ether. In some alternatives herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group. In some alternatives the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the sugar is a glycerol. In some alternatives, the polar head group of the lipid comprises glycerol. In some alternatives, the polar head group of the lipid comprises a phosphate group. In some alternatives, the polar head group of the lipid comprises choline. In some alternatives, the lipid is a phosphatidylethanolomine. In some alternatives, the lipid is a phosphatidylinositol. In some alternatives, the lipid comprises a sphingoid base backbone. In some alternatives, the lipid comprises a sterol lipid, such as cholesterol or its derivatives. In some alternatives, the lipid comprises saccharolipids. In some alternatives, the polar head group comprises choline, phosphate and/or glycerol. In some alternatives, the lipid is a glycolipid. In some alternatives, the lipid comprise a sugar. In some alternatives, the lipid is derived from sphingosine. In some alternatives, the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR. In some alternatives, the cancer is kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone, and brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer. In some alternatives, the cancer is a neuroblastoma, glioblastoma, leukemia or medulloblastoma. In some alternatives, instead of a lipid, an antibody or binding fragment thereof, which comprises a target moiety, is used and such antibody or binding fragment thereof is abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a binding fragment thereof.
- In some alternatives, a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) is provided, wherein the CAR or TCR is bound to a lipid, wherein the lipid comprises a target moiety and the cell comprising the CAR is bound to the target moiety of the lipid. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is a fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol or an aromatic ring. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain, wherein the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid further comprises a spacer group that separates the target moiety from the polar head group. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the cell is a precursor T cell. In some alternatives, the precursor T cell is a hematopoietic stem cell. In some alternatives, the cell is a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of naïve CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. In some alternatives, the cell is a CD4+ T helper lymphocyte cell that is selected from the group consisting of naïve CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and bulk CD4+ T cells. In some alternatives, the lipid is intercalated in a lipid bilayer of a target cell, such as a cancer cell. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell. In some alternatives, the target cell is an immune cell. In some alternatives, the immune cell is a T cell or a B cell. In some alternatives, the target cell is in a tumor microenvironment. In some alternatives, the target cell is a tumor cell of a solid tumor. In some alternatives, the solid tumor is a cancerous tumor, wherein the tumor is from a cancer. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma, liver, colon, skin (including melanoma), bone or brain cancer. In some alternatives, the lipid is a glycerolipid, glycerophospholipid, sphingolipid, sterol lipids, prenol lipid, saccharolipid or a polyketide. In some alternatives, a complex comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) is provided, wherein the CAR or TCR is joined to a lipid, wherein the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar head group and a hydrophobic moiety. In some alternatives, the hydrophobic moiety is a hydrophobic carbon tail. In some alternatives the hydrophobic carbon tail is saturated or unsaturated. In some alternatives, the hydrophobic carbon tail comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 carbons or any number of carbons in between a range set forth in any aforementioned value. In some alternatives, the hydrophobic moiety is a steroid or a cholesterol or comprises an aromatic ring. In some alternatives, the lipid comprises a glycerolipid, glycerophospholipid, sphingolipid, sterol lipid, prenol lipid, saccharolipid or polyketide. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the lipid contains branched alkyl tails. In some alternatives, the lipid can be a sphingolipid. The sphingolipid can contain a backbone of sphingoid bases, such as a set of aliphatic amino alcohols that includes sphingosine. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. In some alternatives, the lipid is a glycosphingolipid. As provided herein, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group comprises a fatty acid such as an aliphatic chain. The fatty acid can be saturated or unsaturated depending on the desired embodiments. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the lipid is a single chain alkylphospholipid. In some alternatives, the lipids comprise a structure of synthetic alkylphospholipids such as edelfosine, perifosine or erucylphosphocholine. In some alternatives, the lipid is a lysophosphatidylcholine, edelfosine, erucylphosphocholine, D-21805 or perifosine. Such lipids are described for example, in van der Lui et al (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety). In some alternatives of the lipids described herein, a choline within the polar head group can be substituted with a piperidine moiety. In some alternatives, the lipid is an anticancer alkylphospholipid. Anticancer phospholipids are described by vander Lui et al. (“A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells” Mol Cancer Ther 2007; 6(8), 2007; incorporated by reference in its entirety). In some alternatives, the lipids provided herein are synthetic and structurally related antitumor agents that can act on cell membranes. These types of synthetic lipids are alkylphospholipids and are described by van Blitterswijk et al. (“Anticancer mechanisms and clinical application of alkylphopholipids” Biochimica et Biophysica Acta 1831 (2013)663-674; incorporated by reference in its entirety herein). Without being limiting the synthetic alkylphospholipids can include edelfosine, miltefosine, perifosine, erucylphosphocholine and/or Erufosine. In some alternatives, the lipid is edelfosine, miltefosine, perifosine, erucylphosphocholine or Erufosine. In some alternatives, the lipid is a stable analog of lysophosphatidylcholine. In some alternatives, the lipid is a thio-ether variant of edelfosine, 1-hexadecylthio- 2-methoxymethyl-rac-glycero-3-phosphocholine. In some alternatives, the lipid is LysoPC, edelfosine, Ilmofosine, Miltefosine, Perifosine, Erucylphophocholine, or Erufosine. In some alternatives herein, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid comprises a target moiety and the CAR is joined to said lipid through an interaction with said target moiety. In some alternatives, the lipid comprises a polar-head group and a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the lipid is a phospholipid ether. In some alternatives herein, a complex is provided, wherein the complex comprises a lipid. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group. In some alternatives the polar head group comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the polar head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the sugar is a glycerol. In some alternatives, the polar head group of the lipid comprises glycerol. In some alternatives, the polar head group of the lipid comprises a phosphate group. In some alternatives, the polar head group of the lipid comprises choline. In some alternatives, the lipid is a phosphatidylethanolomine. In some alternatives, the lipid is a phosphatidylinositol. In some alternatives, the lipid comprises a sphingoid base backbone. In some alternatives, the lipid comprises a sterol lipid, such as cholesterol or its derivatives. In some alternatives, the lipid comprises saccharolipids. In some alternatives, the polar head group comprises choline, phosphate and/or glycerol. In some alternatives, the lipid is a glycolipid. In some alternatives, the lipid comprises a sugar. In some alternatives, the lipid is derived from sphingosine. In some alternatives, the lipid is a glycerol-glycolipid or a sphingo-glycolipid. In some alternatives, the lipid is an ether lipid with branched hydrophobic chains. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the lipid further comprises a target moiety which interacts with the CAR or TCR. In some alternatives, the cancer is kidney, uterine, colon, lung, liver, breast, renal, prostate, ovarian, skin (including melanoma), bone cancer, brain cancer, adenocarcinoma, pancreatic cancer, chronic myelogenous leukemia or leukemia. In some alternatives, the cancer is breast, ovarian, lung, pancreatic, prostate, melanoma, renal, pancreatic, glioblastoma, neuroblastoma, medulloblastoma, sarcoma or liver cancer. In some alternatives, an antibody or binding fragment thereof conjugated to a target moiety is used and said antibody or binding fragment thereof can include abagovomab, abituzumab, adecatumumab, afutuzumab, alacizumab pegol, alemtuzumab, altumomab pentetate, amatuximab, anatumomab mefanetox, anetumab ravtansine, apolizumab, arcitumomab, ascrinvacumab, aselizumab, atezolizumab, atlizumab, avelumab, bapineuzumab, bavituximab, bectumomab, belimumab, besilesomab, bevacizumab, bivatuzumab mertansine, blinatumomab, blontuvetmab, brentuximab, brontictuzumab, cantuzumab mertansine, cantuzumab ravansine, capromab pendetide, carlumab, carotuximab, catumaxomab, cBR96-doxorubicin immunoconjugate, cedelizumab, certolizumab pegol, cetuximab, cidfusituzumab, cidtuzumab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, codrituzumab, coltuximab ravtansine, conatumumab, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denintuzumab mafodotin, denosumab, depatuxizumab mafodotin, derlotuximab biotin, detumomab, dinutuximab, drozitumab, duligotumab, durvalumab, dusigitumab, duvortuxizumab, ecromeximab, eculizumab, edrecolomab, efalizumab, elgemtumab, elotuzumab, emactuzumab, emibetuzumab, enavatuzumab, enfortumab vedotin, enoblituzumab, enoticumab, ensituximab, epratuzumab, erlizumab, ertumaxomab, etaracizumab, farletuzumab, FBTA05, femzumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, futuximab, galiximab, ganitumab, gemtuzumab ozogamicin, girentuximab, glembatumumab vedotin, ibritumomab, icrucumab, igovomab, IMAB362, imalumab, imgatuzumab, indatuximab ravtansine, indusatumab vedotin, intetumumab, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, isatuzimab, labetuzumab, lambrolizumab, lexatumumab, lifastuzumab vedotin, lilotomab satetraxetan, lintuzumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, lumretuzumab, mapatumumab, margetuximab, matuzumab, mepolizumab, milatuzumab, minretumomab, mirvetuximab soravtansine, mitumomab, mogamulizumab, moxetumomab pasudotox, nacolomab tafenatox, naptumomab estafenatox, narnatumab, natalizumab, necitumumab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, obinutuzumab, ocaratuzumab, ocrelizumab, ofatumumab, olaratumab, omalizumab, onartuzumab, ontuxizumab, oportuzumab monatox, oregovomab, otlertuzumab, panitumumab, pankomab, parsatuzumab, pascolizumab, pasotuxizumab, patritumab, pecfusituzumab, pectuzumab, pembrolizumab, pemtumomab, pertuzumab, pexelizumab, pidilizumab, pinatuzumab vedotin, pintumomab, polatuzumab vedotin, pritumumab, racotumomab, radretumab, ramucirumab, ranibizumab, reslizumab, rilotumumab, rituximab, robatumumab, rovelizumab, ruplizumab, sacituzumab govitecan, samalizumab, satumomab pendetide, seribantumab, sibrotuzumab, SGN-CD19A, SGN-CD33A, simtuzumab, siplizumab, siltuximab, sofituzumab vedotin, solitomab, sontuzumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tamtuvetmab, taplitumomab paptox, tarextumab, tenatumomab, teprotumumab, TGN1412, ticilimumab (tremelimumab), tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tovetumab, trastuzumab, TRB S07, tremelimumab, tucotuzumab celmoleukin, tucusituzumab, ublituximab, ulocuplumab, urelumab, urtoxazumab, ustekinumab, vandortuzumab vedotin, vantictumab, vanucizumab, veltuzumab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumamab, zanolimumab, zatuximab, cosfroviximab, diridavumab, exbivirumab, felvizumab, foravirumab, larcaviximab, libivirumab, motavizumab, motovizumab, nolovizumab, numavizumab, palivizumab, porgaviximab, PRO 140, rafivirumab, ralivizumab, regavirumab, reslivizumab, resyvizumab, sevirumab, suvizumab, tuvirumab, umavizumab, edobacomab, nebacumab, pagibaximab, panobacumab, raxibacumab, or tefibazumab or a binding fragment thereof. In some alternatives, the CAR comprises an scFv.
- In some alternatives, a method of treating, ameliorating, or inhibiting a cancer in a subject is provided, the method comprising: a) introducing, providing, or administering to a subject a composition that comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying a subject in need of a therapy for cancer prior to steps a-c. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as an aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinotrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the masking moiety is removed when the composition is within an acidic environment. In some alternatives, the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values. In some alternatives, the masking moiety is removed by nitrosylation. In some alternatives, the cell is provided to the subject the cell is provided to the
subject subject - In some alternatives, a composition is provided, wherein the composition comprises a lipid, wherein the lipid comprises a target moiety that is bound to a masking moiety. In some alternatives, the target is bound to the masking moiety through a spacer. In some alternatives, the masking moiety is removed when the composition is in a tumor microenvironment. In some alternatives, the masking moiety is removed when the composition is in a ROS rich tumor environment. In some alternatives, the masking moiety is removed when the composition is within an acidic environment. In some alternatives, the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values. In some alternatives, the masking moiety is removed by nitrosylation. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor.
- In some alternatives, a method of treating, ameliorating, or inhibiting a cancer in a subject is provided, wherein the method comprises a) introducing, providing, or administering to a subject the composition of any one of the alternatives herein, wherein the composition comprises a lipid, which comprises a target moiety that is bound to a masking moiety and, optionally, by attachment through a spacer, b) introducing, providing, or administering to said subject a cell comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR), which is specific for the target moiety once the masking moiety is removed from the target moiety, c) removing the masking moiety from the target moiety thereby allowing the target moiety to bind to the CAR present on the cell, and, d) optionally, measuring or evaluating the binding of the cell comprising the CAR to the lipid, after steps a-c and/or e) optionally, measuring or evaluating the treatment, amelioration, or inhibition of said cancer after steps a-d, and/or f) optionally, identifying a subject in need of a therapy for cancer prior to steps a-c. In some alternatives, the lipid targets a cell, such as a cancer cell or a tumor cell, or a tumor. In some alternatives, the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is fatty acid such as a aliphatic chain. In some alternatives, the fatty acid is saturated or unsaturated. In some alternatives, the hydrophobic group comprises an alkyl, alkenyl or alkynyl group. In some alternatives, the hydrophobic group comprises a terpenoid lipid such as a steroid or cholesterol. In some alternatives, the hydrophobic group comprises an ether linkage, wherein the ether linkage is between the polar head group and the aliphatic chain. In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group, an oligosaccharide residue, a sugar residue, phosphatidyl serine or phosphatidyl inositol. In some alternatives, the sugar is a glycerol. In some alternatives, the target moiety is a hapten, poly(his) tag, Strep-tag, FLAG-tag, V5-tag, Myc-tag, HA-tag, NE-tag, biotin, digoxigenin, dinitrophenol or fluorescein. In some alternatives, the hydrophobic group comprises a carbon alkyl chain. In some alternatives, the carbon alkyl chain comprises 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 carbons or any number that is within a range defined by any two aforementioned values. In some alternatives, the carbon alkyl chain comprises 8-22 carbons, such as 8-12, 12-14, 14-16, or 16-22 carbons. In some alternatives, the polar-head group comprises phosphocholine, a piperidine moiety or a trimethylarseno-ethyl-phosphate moiety. In some alternatives, the spacer comprises a PEG spacer, a hapten (2x) spacer, or an alkane chain. In some alternatives, the PEG spacer comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 PEG molecules, or any amount of PEG molecules that is within a range defined by any two aforementioned values. In some alternatives, the masking moiety comprises a phenolic hydroxyl group or PEG. In some alternatives, the phenolic hydroxyl group is bound to a hydroxyl on a xanthene moiety of fluorescein. In some alternatives, the masking moiety is bound to the target moiety by a cleavable moiety, which is optionally configured to be specifically cleavable in a tumor microenvironment. In some alternatives, the masking moiety is removed when the composition is within an acidic environment. In some alternatives, the acidic environment comprises a pH of 4, 5, 6 or 6.5 or any pH in between a range defined by any two aforementioned values. In some alternatives, the masking moiety is removed by nitrosylation. In some alternatives, the cleavable moiety, which is configured to be cleavable in a tumor microenvironment, is cleaved by a reactive oxygen species reaction, an acidic pH, hypoxia, or nitrosylation. In some alternatives, the cell is provided to the subject the cell is provided to the
subject subject - It is understood that the examples and alternatives described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of any appended claims.
- With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.
- It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to alternatives containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”
- In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.
- Any of the features of an embodiment of the first through ninth aspects is applicable to all aspects and embodiments identified herein. Moreover, any of the features of an embodiment of the first through ninth aspects is independently combinable, partly or wholly with other embodiments described herein in any way, e.g., one, two, or three or more embodiments may be combinable in whole or in part. Further, any of the features of an embodiment of the first through ninth aspects may be made optional to other aspects or embodiments.
Claims (19)
1. A complex comprising: a chimeric antigen receptor (CAR) or a T cell receptor (TCR); and a compound comprising a lipid, wherein the lipid comprises a hydrophobic group, a polar head group, and a target moiety; wherein the CAR or TCR is specifically bound to the target moiety.
2. The complex of claim 1 , wherein the hydrophobic group comprises a fatty acid.
3. The complex of claim 1 , wherein the hydrophobic group comprises a C8-22 alkyl group.
4. The complex of claim 1 , wherein the hydrophobic group comprises a terpenoid lipid.
5. The complex of claim 1 , wherein the lipid comprises an ether linkage, wherein the ether linkage is between the polar head group and the hydrophobic group.
6. The complex of claim 5 , wherein the lipid is a phospholipid ether.
7. The complex of claim 1 , wherein the polar head comprises a group selected from choline, phosphatidylcholine, sphingomyelin, phosphoethanolamine, an oligosaccharide residue, a sugar residue, glycerol, phosphatidyl serine, phosphatidyl inositol, phosphocholine, piperidine moiety, or a trimethylarseno-ethyl-phosphate.
8. The complex of claim 1 , wherein the target moiety is selected from the group consisting of a hapten, a poly(his) tag, a strep-tag, a FLAG-tag, a V5-tag, a myc-tag, an HA-tag, an NE-tag, a biotin, a digoxigenin, a dinitrophenol, a fluorescein, and a derivative thereof.
9. The complex of claim 8 , wherein the target moiety comprises a fluorescein or a derivative thereof.
10. The complex of claim 1 , wherein the lipid further comprises a spacer between the target moiety and the polar head group, wherein the spacer is selected from the group consisting of poly(carboxybetaine), peptide, polyglycidol, polyethylene, polyanhydride, polyphosphoester, polycaprolactone, polyethylene glycol (PEG), a hapten (2x), and an alkane chain.
11. The complex of claim 10 , wherein the PEG spacer comprises from 1 to 21 PEG subunits.
13. A cell comprising the complex of claim 1 , wherein the CAR or TCR is expressed on the surface of the cell, or the lipid is intercalated in a lipid bilayer of the cell.
14. The cell of claim 13 , wherein the cell is selected from a precursor T cell, a hematopoietic stem cell, a CD8+ T cell, or a CD4+ T cell, a tumor cell, an immune cell, a T cell, or a B cell.
16. A complex comprising an antibody or an antigen binding fragment thereof comprising a target moiety, a chimeric antigen receptor (CAR) or a T cell receptor (TCR) specifically bound to the target moiety, wherein an antibody or an antigen binding fragment thereof is specific for an antigen present on a cancer cell, virus, or bacterial cell.
17. The complex of claim 16 , wherein the target moiety is selected from the group consisting of a hapten, a poly(his) tag, a strep-tag, a FLAG-tag, a V5-tag, a myc-tag, an HA-tag, an NE-tag, a biotin, a digoxigenin, a dinitrophenol, a fluorescein, and a derivative thereof; and wherein the CAR or TCR is expressed on the surface of a cell selected from a precursor T cell, a hematopoietic stem cell, a CD8+ T cell, or a CD4+ T cell, a tumor cell, an immune cell, a T cell, or a B cell.
18. A method of treating, ameliorating, or inhibiting a cancer in a subject comprising:
a) administering to the subject a composition comprising an antibody or antigen binding fragment thereof comprising a target moiety; and
b) administering to the subject a cell comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) capable of specifically binding to the target moiety.
19. The method of claim 18 , wherein the target moiety is selected from the group consisting of a hapten, a poly(his) tag, a strep-tag, a FLAG-tag, a V5-tag, a myc-tag, an HA-tag, an NE-tag, a biotin, a digoxigenin, a dinitrophenol, a fluorescein, and a derivative thereof; and wherein the cell is selected from a precursor T cell, a hematopoietic stem cell, a CD8+ T cell, or a CD4+ T cell, a tumor cell, an immune cell, a T cell, or a B cell.
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2018
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- 2018-02-06 AU AU2018219226A patent/AU2018219226A1/en active Pending
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- 2018-02-06 US US16/480,833 patent/US11649288B2/en active Active
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AU2018219226A1 (en) | 2019-08-15 |
US20200087399A1 (en) | 2020-03-19 |
CA3051481A1 (en) | 2018-08-16 |
EP3579870A4 (en) | 2020-12-30 |
WO2018148224A1 (en) | 2018-08-16 |
CN110612119A (en) | 2019-12-24 |
EP3579870A1 (en) | 2019-12-18 |
US11649288B2 (en) | 2023-05-16 |
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