WO2018160622A1 - Compositions and methods for car t cell therapy - Google Patents

Compositions and methods for car t cell therapy Download PDF

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Publication number
WO2018160622A1
WO2018160622A1 PCT/US2018/020095 US2018020095W WO2018160622A1 WO 2018160622 A1 WO2018160622 A1 WO 2018160622A1 US 2018020095 W US2018020095 W US 2018020095W WO 2018160622 A1 WO2018160622 A1 WO 2018160622A1
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Prior art keywords
car
cancer
clauses
cells
patient
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PCT/US2018/020095
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English (en)
French (fr)
Inventor
Philip Stewart Low
Haiyan CHU
Yong Gu Lee
Yingjuan J. LU
Christopher Paul Leamon
Leroy W. WHEELER II
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Purdue Research Foundation
Endocyte Inc
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Purdue Research Foundation
Endocyte Inc
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Publication date
Priority to US16/489,455 priority Critical patent/US11850262B2/en
Priority to EP24199482.1A priority patent/EP4501352A3/en
Priority to EP18761400.3A priority patent/EP3589295B1/en
Priority to JP2019547107A priority patent/JP7178355B2/ja
Priority to CN201880028009.XA priority patent/CN110582288B/zh
Priority to ES18761400T priority patent/ES3010559T3/es
Application filed by Purdue Research Foundation, Endocyte Inc filed Critical Purdue Research Foundation
Publication of WO2018160622A1 publication Critical patent/WO2018160622A1/en
Anticipated expiration legal-status Critical
Priority to US16/921,400 priority patent/US11759480B2/en
Priority to JP2022181982A priority patent/JP7585280B2/ja
Priority to US18/494,613 priority patent/US20240165159A1/en
Priority to JP2024194196A priority patent/JP2025024006A/ja
Ceased legal-status Critical Current

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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
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    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
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    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
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    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
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    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/033—Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the internal surface of the plasma membrane, e.g. containing a myristoylation motif

Definitions

  • the present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker.
  • the disclosure also relates to compositions for use in such methods.
  • Immunotherapy based on adoptive transfer of lymphocytes (e.g., T cells) into a patient is a valuable therapy in the treatment of cancer and other diseases.
  • Important advancements have been made in the development of immunotherapies based on adoptive transfer of lymphocytes.
  • T cells expressing chimeric antigen receptors (CAR T cells).
  • the chimeric antigen receptor (CAR) is a genetically engineered receptor that is designed to target a specific antigen, for example, a tumor antigen. This targeting can result in cytotoxicity against the tumor, for example, such that CAR T cells expressing CARs can target and kill tumors via the specific tumor antigens.
  • First generation CARs are composed of a recognition region, e.g., a single chain fragment variable (scFv) region derived from an antibody for recognition and binding to the antigen expressed by the tumor, and an activation signaling domain, e.g., the ⁇ 3 ⁇ chain of T cells can serve as a T cell activation signal in CARs.
  • a recognition region e.g., a single chain fragment variable (scFv) region derived from an antibody for recognition and binding to the antigen expressed by the tumor
  • an activation signaling domain e.g., the ⁇ 3 ⁇ chain of T cells can serve as a T cell activation signal in CARs.
  • a co- stimulation domain e.g., CD137, CD28 or CD 134
  • second generation CARs to achieve prolonged activation of T cells in vivo.
  • Addition of a co-stimulation domain enhances the in vivo proliferation and survival of T cells containing CARs, and initial clinical data have shown that such constructs are promising therapeutic agents in the treatment of diseases, such as cancer.
  • CAR T cell therapies Although improvements have been made in CAR T cell therapies, several problems remain. First, 'off-target' toxicity may occur due to normal cells that express the antigen targeted by the CAR T cells (e.g., a tumor- associated antigen). Second, unregulated CAR T cell activation may be found where the rapid and uncontrolled elimination of diseased cells (e.g., cancer cells) by CAR T cells induces a constellation of metabolic disturbances, called tumor lysis syndrome, or cytokine release syndrome (CRS), which can be fatal to patients. Tumor lysis syndrome and CRS can result due to administered CAR T cells that cannot be easily regulated, and are activated uncontrollably.
  • diseased cells e.g., cancer cells
  • CRS cytokine release syndrome
  • CAR T cells show great promise as a tool in the treatment of diseases, such as cancer
  • additional CAR T cell therapies are needed that provide reduced off -target toxicity, and more precise control of CAR T cell activation.
  • a small molecule ligand linked to a targeting moiety by a linker is used as a bridge between the cancer and the CAR T cells directing the CAR T cells to the cancer for amelioration of the cancer.
  • the "small molecule ligand” can be, for example, a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, or a CCK2R ligand, each of which is a small molecule ligand that binds specifically to cancer cells (i.e., the receptor for these ligands is overexpressed on cancers compared to normal tissues).
  • the "small molecule ligand” is linked to a "targeting moiety” that binds to the CAR expressed by CAR T cells.
  • the "targeting moiety” can be selected, for example, from 2,4-dinitrophenol (DNP), 2,4,6- trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS-fluorescein, pentafluorophenyl ester (PFP), tetrafluorophenyl ester (TFP), a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6- trinitrophenol
  • biotin biotin
  • digoxigenin fluorescein, fluorescein isothiocyanate
  • FITC fluorescein isothiocyanate
  • NHS-fluorescein pentafluorophenyl ester
  • TFP tetra
  • the "targeting moiety” binds to the recognition region of the genetically engineered CAR expressed by CAR T cells. Accordingly, the recognition region of the CAR (e.g., a single chain fragment variable region (scFv) of an antibody, an Fab, Fv, Fc,(Fab')2 fragment, and the like) is directed to the "targeting moiety.”
  • the small molecule ligand linked to a targeting moiety by a linker acts as a bridge between the cancer and the CAR T cells, directing the CAR T cells to the cancer for amelioration of the cancer.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, ii) administering to the patient a first dose of a CAR T cell composition wherein the CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise the CAR directed to the targeting moiety, and iii) administering to the patient a second dose of the CAR T cell composition wherein the CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise the CAR directed to the targeting moiety.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, and ii) administering to the patient a CAR T cell composition comprising CAR T cells wherein the CAR T cells in the composition comprise the CAR directed to the targeting moiety and wherein the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, ii) administering to the patient a CAR T cell composition wherein the CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise the CAR directed to the targeting moiety, and iii) administering to the patient a folate, a conjugate comprising a folate wherein the conjugate comprising a folate does not comprise a targeting moiety, or an agent that inhibits activation of the CAR T cells.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, and wherein the compound, or the pharmaceutically acceptable salt thereof, is at a dose of about 10 nmoles/kg of body weight of the patient to about 2500 nmoles/kg of body weight of the patient, and ii) administering to the patient a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the CAR T cells are at a dose of about 1 million of the CAR T cells to about 15 million of the CAR T cells.
  • a method of treatment of a cancer is provided.
  • the method comprises i) administering continuously to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, ii) administering to the patient a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety, and iii) ending administration of the compound, or the pharmaceutically acceptable salt thereof, to reduce cytokine release syndrome in the patient.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, wherein at least a first dose and a second dose of the compound, or the pharmaceutically acceptable salt thereof, are administered to the patient, wherein the first dose and the second dose are different, wherein the second dose of the compound, or the pharmaceutically acceptable salt thereof, is about 2-fold to about 15000-fold greater in amount than the first dose of the compound, or the pharmaceutically acceptable salt thereof, and ii) administering to the patient a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker and wherein the compound, or the pharmaceutically acceptable salt thereof, is administered once weekly to the patient, and ii) administering to the patient a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • a method of treatment of a cancer is provided.
  • the method comprises i) administering to a patient a first dose of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, ii) administering to the patient at least a second dose of the compound, or a pharmaceutically acceptable salt thereof, wherein the second dose of the compound, or the pharmaceutically acceptable salt thereof, is at least about 50 percent lower in amount than the first dose of the compound, or the
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • a method of treatment of a cancer comprises i) administering to a patient a first dose of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker and wherein the compound, or the
  • a pharmaceutically acceptable salt thereof is administered to the patient at least about one hour prior to the administration of a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety, ii) then administering to the patient a dose of the CAR T cell composition, and iii) then administering to the patient a second dose of the compound, or the pharmaceutically acceptable salt thereof.
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, and ii) administering to the patient a CAR T cell composition wherein the CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the small molecule ligand is a PSMA ligand and the targeting moiety is FITC.
  • the small molecule ligand linked to a targeting moiety by a linker can have the formula
  • a method of treatment of a cancer comprises i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, and ii) administering to the patient a CAR T cell composition wherein the CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the small molecule ligand is a CAIX ligand and the targeting moiety is FITC.
  • the small molecule ligand linked to a targeting moiety by a linker can have the formula
  • a method of treatment of a cancer comprises i) administering to a patient a first compound, or a pharmaceutically acceptable salt thereof, wherein the first compound, or the pharmaceutically acceptable salt thereof, comprises a PSMA ligand linked to FITC by a linker, ii) administering to the patient a second compound, or a pharmaceutically acceptable salt thereof, wherein the second compound, or the pharmaceutically acceptable salt thereof, comprises a CAIX ligand linked to FITC by a linker, and iii) administering to the patient a CAR T cell composition wherein the CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • the first compound can have the formula
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise the CAR directed to the targeting moiety.
  • the ligand is selected from the group consisting of a folate, DUPA, an NK-IR ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • any one of clauses 1 to 26 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphoma,
  • T cell toxicity to the cancer occurs.
  • the first dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non- transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non-transformed T cells, and about 1: 1 of the CAR T cells to the non- transformed T cells.
  • the second dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non- transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non-transformed T cells, and about 1: 1 of the CAR T cells to the non- transformed T cells.
  • the first dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio of from about 1:1 to about 1:5 of the CAR T cells to the non-transformed T cells.
  • the second dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio of from about 1:1 to 1:5 of the CAR T cells to the non- transformed T cells.
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • CAR T cell composition comprises CAR T cells, wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells.
  • ligand is selected from the group consisting of a folate, DUPA, an NK- IR ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • any one of clauses 56 to 81 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphom
  • CAR has a recognition region and the recognition region of the CAR is a single chain fragment variable (scFv) region of an anti-FITC antibody.
  • scFv single chain fragment variable
  • a compound or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety;
  • a conjugate comprising a folate wherein the conjugate comprising a folate does not comprise a targeting moiety, or an agent that inhibits activation of the CAR T cells.
  • step iii comprises administering a folate.
  • step iii comprises administering folic acid or leucovorin.
  • step iii comprises administering the conjugate comprising a folate.
  • Q is selected from the group consisting of C and CH;
  • X 2 and X 3 are each independently selected from the group consisting of oxygen, sulfur, -C(Z)-, -C(Z)0-, -OC(Z)-, -N(R 4b )-, -C(Z)N(R 4b )-, -N(R 4b )C(Z)-,
  • R 1 is selected-from the group consisting of hydrogen, halo, d-C 12 alkyl, and
  • R 2 , R 3 , R 4 , R 4a , R 4b , R 5 , R 5b , R 6b , and R 7b are each independently selected from the group consisting of hydrogen, halo, Ci-C 12 alkyl, Ci-C 12 alkoxy, Ci-Ci 2 alkanoyl, Ci-C 12 alkenyl, Ci-C 12 alkynyl, (Ci-Ci 2 alkoxy)carbonyl, and (Ci-C 12 alkylamino)carbonyl;
  • R 6 and R 7 are each independently selected from the group consisting of hydrogen, halo, Ci-Ci 2 alkyl, and Ci-Ci 2 alkoxy; or, R 6 and R 7 are taken together to form a carbonyl group;
  • R 6a and R 7a are each independently selected from the group consisting of hydrogen, halo, Ci-Ci 2 alkyl, and Ci-Ci 2 alkoxy; or R 6a and R 7a are taken together to form a carbonyl group;
  • p, r, s, and t are each independently either 0 or 1;
  • * represents an optional covalent bond to the rest of the conjugate, if any additional chemical moieties are part of the folate.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein NHS -fluorescein
  • pentafluorophenyl ester tetrafluorophenyl ester
  • a knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an inte ⁇ ⁇ er from 0 to 200.
  • n is an integer from 0 to 150.
  • n is an integer from 0 to 110.
  • n is an integer from 0 to 20.
  • n is an integer from 15 to 20.
  • n is an integer from 15 to 110.
  • any one of clauses 108 to 134 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphom
  • CAR T cell composition are administered. 147.
  • T cell toxicity to the cancer occurs.
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • T cells comprise a polypeptide comprising SEQ ID NO:2.
  • the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non-transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non- transformed T cells, and about 1:1 of the CAR T cells to the non-transformed T cells.
  • the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non-transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non- transformed T cells, and about 1:1 of the CAR T cells to the non-transformed T cells.
  • the CAR T cell composition comprises a mixture
  • the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells in a ratio of from about 1:1 to about 1:5 of the CAR T cells to the non- transformed T cells.
  • T cell composition comprises a mixture comprising about 10 million of the CAR T cells and about 40 million of the non-transformed T cells.
  • the agent that inhibits activation of the CAR T cells is selected from the group consisting of a lymphocyte-specific protein tyrosine kinase inhibitor, a PI3 kinase inhibitor, an inhibitor of an IL-2 inducible T cell kinase, a JAK inhibitor, a BTK inhibitor, EC2319, and an agent that blocks CAR T cell binding to the compound, or the pharmaceutically acceptable salt thereof, but does not bind to the cancer.
  • the dose of the CAR T cells administered to the patient in the CAR T cell composition is selected from the group consisting of about 1 million, about 2 million, about 3 million, about 4 million, about 5 million, about 6 million, about 7 million, about 8 million, about 9 million, about 10 million, about 11 million, about 12 million, about 12.5 million, about 13 million, about 14 million, and about 15 million of the CAR T cells.
  • fluoresceinamine FITC
  • sodium fluorescein sodium fluorescein
  • a method of treatment of a cancer comprising
  • a compound, or a pharmaceutically acceptable salt thereof wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, and wherein the compound, or the pharmaceutically acceptable salt thereof, is at a dose of about 10 nmoles/kg of body weight of the patient to about 2500 nmoles/kg of body weight of the patient;
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the CAR T cells are at a dose of about 1 million of the CAR T cells to about 15 million of the CAR T cells.
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • the targeting moiety is FITC.
  • the linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • any one of clauses 183 to 201 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lympho
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • a method of treatment of a cancer comprising
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • FITC fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester a knottin
  • a centyrin and a DARPin.
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200. 223.
  • the linker comprises PEG and the targeting moiety is FITC, or a pharmaceutically acceptable salt thereof.
  • any one of clauses 215 to 232 wherein the administration is by intravenous administration.
  • the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic
  • T cell toxicity to the cancer occurs.
  • 240 The method of any one of clauses 215 to 238 wherein off-target tissue toxicity does not occur in the patient and wherein CAR T cell toxicity to the cancer occurs.
  • T cell composition further comprises non-transformed T cells.
  • the CAR T cell composition further comprises non-transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non-transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non- transformed T cells, about 1:2 of the CAR T cells to the non-transformed T cells, and about 1:1 of the CAR T cells to the non-transformed T cells.
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker and wherein the compound, or the pharmaceutically acceptable salt thereof, is administered once weekly to the patient; and
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • the ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an N G2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200. 260. The method of any one of clauses 252 to 259 wherein the linker comprises PEG and the targeting moiety is FITC, or a pharmaceutically acceptable salt thereof.
  • any one of clauses 252 to 270 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphom
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • T cells comprise a polypeptide comprising SEQ ID NO:2.
  • T cell composition further comprises non-transformed T cells.
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, wherein at least a first dose and a second dose of the compound, or the pharmaceutically acceptable salt thereof, are administered to the patient, wherein the first dose and the second dose are different, wherein the second dose of the compound, or the pharmaceutically acceptable salt thereof, is about 2-fold to about 15000-fold greater in amount than the first dose of the compound, or the pharmaceutically acceptable salt thereof; and
  • CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphom
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • a method of treatment of a cancer comprising i) administering to a patient a first dose of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • the linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof. 371. The method of any one of clauses 325 to 370 wherein the linker comprises PEG.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • n is an integer from 0 to 110.
  • n is an integer from 0 to 20.
  • any one of clauses 325 to 378 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lympho
  • T cell toxicity to the cancer occurs.
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • T cells comprise a polypeptide comprising SEQ ID NO:2.
  • fluoresceinamine sodium fluorescein, or fluorescein.
  • a method of treatment of a cancer comprising i) administering to a patient a first dose of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker and wherein the compound, or the
  • CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety;
  • T cell toxicity to the cancer occurs.
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • n is an integer from 0 to 150.
  • n is an integer from 15 to 110.
  • any one of clauses 406 to 447 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lympho
  • CAR has a recognition region and the recognition region is a single chain fragment variable (scFv) region of an anti-FITC antibody, wherein the CAR has a co-stimulation domain and the co- stimulation domain is CD137 (4-1BB), and wherein the CAR has an activation signaling domain and the activation signaling domain is a T cell CD3 ⁇ chain.
  • scFv single chain fragment variable
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker; and
  • CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety; and wherein the small molecule ligand is a PSMA ligand and the targeting moiety is FITC.
  • a method of treatment of a cancer comprising
  • CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety; and wherein the small molecule ligand is a CAIX ligand and the targeting moiety is FITC.
  • a method of treatment of a cancer comprising i) administering to a patient a first compound, or a pharmaceutically acceptable salt thereof, wherein the first compound, or the pharmaceutically acceptable salt thereof, comprises a PSMA ligand linked to FITC by a linker;
  • pharmaceutically acceptable salt thereof comprises a CAIX ligand linked to FITC by a linker
  • CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • FIGURES 1A-B show anti-FITC CAR T cell mediated toxicity.
  • Figure 1A shows the changes in bodyweight for the mice of different treatment groups.
  • Figure IB shows the detected concentration of IFN-gamma for the different treatment groups.
  • Figure 1C shows the first- week survival (%) of the mice in the different treatment groups.
  • FIGURES 2A-B show the effect of anti-FITC CAR T cell regulation on the tumor response.
  • Figure 2A shows tumor growth for mice that are treated with either CAR T cells and PBS or CAR T cells and FITC-Folate.
  • Figure 2B shows a summary of the tumor response results for mice used in the study.
  • FIGURES 3A-D show the effect of FITC-Folate concentration on the tumor response.
  • Figure 3A shows the detected concentration of IFN-gamma at the different FITC- folate concentrations.
  • Figure 3B shows post CAR T cell injection tumor growth in the presence of different FITC-folate concentrations.
  • Figure 3C shows the first-week survival (%) of the mice.
  • Figure 3D shows a summary of the tumor response results for the mice used in the study.
  • FIGURES 4A-B show suppressing FITC CAR T cell activation with agents that inhibit a mediator of T cell activation signal.
  • Figure 4A shows the changes in IFN- gamma concentration as a function of agent concentration.
  • Figure 4B shows the changes in CD69 expression as a function of agent concentration.
  • FIGURE 5 shows a general diagram of the constructs used for CAR T transduction.
  • FIGURES 6A-D show anti-tumor efficacy and toxicity at different EC 17 doses and numbers of CART cells.
  • Figure 6A shows tumor volume over time.
  • Figure 6B shows body weight changes over time.
  • Figure 6C shows the maximal percentage body weight loss for each EC 17 dose.
  • Figure 6D shows the percentage of mice showing sCRS (cytokine release syndrome) for each EC17 dose.
  • sCRS cytokine release syndrome
  • FIGURE 7 shows the rescue with EC0923 of mice having sCRS and observed responses of mice treated with or without EC0923, and harvested organs from mice treated with or without EC0923.
  • FIGURES 8A-D show anti-tumor efficacy and toxicity of different CAR T doses.
  • Figure 8 A shows tumor volume over time.
  • Figure 8B shows body weight changes over time.
  • Figure 8C shows the maximal percentage of body weight loss for each CAR T dose.
  • Figure 8D shows the percentage of mice showing sCRS for each CAR T dose.
  • FIGURES 9A-B show anti-tumor efficacy and body weight change for different EC 17 doses.
  • Figure 9A shows tumor volume over time.
  • Figure 9B shows body weight change over time.
  • FIGURES lOA-C show anti-tumor efficacy of different CAR T cell and non- transformed T cell mixtures.
  • Figure 10A shows tumor volume over time; ( ⁇ ) no CAR-T, (o) CAR-T on Day 0, ( ⁇ ) CAR-T on Day 0, unmodified T on Day 52, (T ) CAR-T on Day 0, Day 46 and Day 52.
  • Figure 10B shows body weight change over time; ( ⁇ ) no CAR-T, (o) CAR-T on Day 0, ( ⁇ ) CAR-T on Day 0, unmodified T on Day 52, (T ) CAR-T on Day 0, Day 46 and Day 52.
  • Figure IOC shows the amount of CAR T cells in blood and tumor volume for different CAR T cell and non-transformed T cell mixtures.
  • FIGURES 11 A-B show anti-tumor efficacy and toxicity of 5 million CAR T cells and different EC 17 dosing schedules.
  • Figure 11A shows tumor volume over time.
  • Figure 1 IB shows body weight change over time.
  • FIGURE 12 shows control of CAR T cell mediated toxicity via regulation of CAR T cell activation by the use of competitors to inhibit CAR T cell activation and by ending administration of the bridge.
  • FIGURES 13A-C show the results of a FITC-Folate dose escalation study.
  • Figure 13A shows the percent body weight change over time after administration of the bridge and the CAR T cells.
  • Figure 13B shows the change in tumor volume over time after injection of CAR T cells and the bridge.
  • Figure 13C shows the percent of survival after the first week of treatment with the bridge and the CAR T cells.
  • FIGURES 14A-B show the effect of the FITC-ligand bridge molecule on CAR T cell proliferation and cytokine production.
  • Figure 14A shows the number of CAR T cells 6 days after the introduction of the CAR T cells into mice.
  • Figure 14B shows the concentration of the serum cytokines IL-2, IFN- ⁇ , and TNF-a 6 days after the introduction of CAR T cells into mice.
  • FIGURE 15 shows the concentration of IFN- ⁇ as a function of the concentration of FITC -folate in an in vitro assay.
  • FIGURE 16 shows the rescue (based on a measurement of cytokine production) with EC0923 or fluorescein or mice having cytokine release syndrome.
  • FIGURE 17 shows that CAR-T cell activity (based on a measurement of cytokine production) is dependent on the presence of the tumor and on EC 17 dose level.
  • FIGURES 18 A-C show that CAR-T cells do not proliferate in naive mice with no tumors.
  • Figure 18A shows body weight change in mice (with no tumors) injected with CAR-T cells, but no EC 17 or with 500 nmoles/kg of EC 17 three times weekly.
  • Figures 18B and C show CAR-T cell number and spleen size in these mice versus mice with HEK (folate - receptor positive) tumors.
  • the left-hand bar in each group of three bars is mice without tumors injected with no EC 17 but with CAR-T cells
  • the middle bar is mice without tumors injected with CAR-T cells and EC 17
  • the right-hand bar is mice with tumors injected with CAR-T cells and EC17.
  • N.D. is not determined and the y-axis is logarithmic for Figure 18.
  • FIGURES 19A-B show effects on tumor size of CAR-T cells and EC 17 injected into mice using an MDA-MB-231 model (high folate receptor expression levels - Figure 19A) or an OV90 tumor model (low folate receptor expression levels - Figure 19B).
  • FIGURES 20A-B show effects on tumor size (Figure 20A) and body weight loss (Figure 20B) of CAR-T cells and various doses of EC 17 injected into mice using an MDA-MB-231 model.
  • FIG. 21 A and 21B show FITC-CAR-T anti-tumor activity in a MDA-MB-231 model.
  • FIG. 22A and 22B show FITC-CAR-T anti-tumor activity in an OV-90 model.
  • FIG. 23A and 23B show FITC-CAR-T anti-tumor activity in a KB model.
  • 2/3 had sCRS on day 23 and 1/3 had sCRS on day 37.
  • FIG. 24A and 24B show FITC-CAR-T anti-tumor activity in a HEK-FRa model.
  • FIG. 25A and 25B show FITC-CAR-T anti-tumor activity in a SKOV-3 model.
  • Panels A and B show the protocol for treatment.
  • Panel D shows the effect of EC 17 pre-painting on tumor size.
  • FIG. 27, Panel A shows the protocols for treatment.
  • Panel B shows toxicity studies.
  • Panel C shows the effect of EC17 pre-painting on tumor toxicity.
  • Linel no EC17.
  • Line 2 EC17 4h pre-done.
  • Line 4 EC 17 48h post CAR-Ts.
  • FIG. 28 Panels A-D, show CAR-T cell number in blood. CAR-T number in mice without rescue was considered as 1.
  • FIG. 29, Panels A-E show comparison studies of three rescue agents (folic acid, sodium fluorescein (NAFL), and leucovorin).
  • FIG. 30A and 30B show rescue assays. Mice with fluorescein rescue had the least body weight loss. All mice with rescue reached complete response, except 2/9 in the fluorescein rescue group. Line 1 no EC17. Line 2: no EC17 but Fluorescein. Line 3: Fluorescein rescue. Line 4: Leucovorin rescue. Line 5: Folic acid rescue. Line 6: no rescue.
  • FIG. 31 shows a sodium fluorescein (60 umol/kg) rescue study schema.
  • FIG. 32A and 32B show NaFL rescue related organ weight changes. (1) CAR-T; (2) CAR-T + EC17; (3) CAR-T + EC17 + NaFL rescue.
  • FIG. 33 Panels A-G, show cytokine production in mouse blood 7 hours after
  • FIG. 34 Panels A-G, show cytokine production in mice (27 hours after NaFL rescue).
  • FIG. 35 Panels A-E, show cytokine production reduced in mouse blood ( ⁇ 7 hours after NaFL rescue).
  • FIG. 36A and 36B show NaFL rescue effect on FITC CAR-T anti-tumor activity and body weight change. (1) CAR-T only; (2) CAR-T + EC17; (3) CAR-T + EC17 + NaFL.
  • FIG. 37A and 37B show the effect of rescue on cytokine levels.
  • FIG. 38A shows a CAR-T administration schedule.
  • FIG. 38B shows body weight changes.
  • FIG. 39 Panels A-D, show that cytokine production in blood is CAR-T dose dependent.
  • FIG. 40A shows the dosing schedule and FIG. 40B shows that CAR-T number in blood is EC 17 dose dependent (day 3 in vivo).
  • FIG. 41 A shows the dosing schedule and FIG. 4 IB shows that CAR-T count in blood is EC 17 dose dependent although the difference is smaller (day 6 in vivo).
  • FIG. 42 shows mouse body weight changes following CAR-T and EC 17 injection.
  • FIG. 43A and 43B show CAR-T cell count and spleen size in mice post CAR- T cell and EC 17 injection.
  • Mice with tumor CAR-T 5 million + EC 17 SIW;
  • naive mice CAR-T 8 million no EC 17;
  • naive mice CAR-T 8 million + EC 17 TIW;
  • naive mice CAR-T 5 million no EC 17;
  • FIG. 44 shows cytokine production following EC 17 and CAR-T cell injection in the presence and absence of a tumor.
  • FIG. 45 shows the universality of anti-FITC CAR T cell therapy: binding of various adaptors to CAR T cells.
  • FIG. 46 shows that the universal Car T cell can eliminate various cancer cells expressing orthogonal antigens upon addition of antigen matched bridges in vitro.
  • FIG. 47 shows the relationship between concentration of bridges and the universal CAR T cell's anti-tumor activity in vitro.
  • FIG. 48 shows that the universal CAR T cell can eliminate various cancer cells expressing orthogonal antigens upon addition of antigen matched bridges in vivo.
  • FIG. 49 shows that the universal CAR T cell can eliminate two tumors via cocktail of bridges in vivo.
  • FIG. 50 shows a sodium fluorescein (0.06, 0.6, 6 umol/kg) rescue study schema.
  • FIG. 51 A shows anti-tumor activity (6 umol/kg NaFL rescue).
  • FIG. 5 IB shows the corresponding body weight changes.
  • FIG. 52 Panels A-E, show cytokine levels in mouse blood following sodium fluorescein rescue.
  • FIG. 53 Panel A shows a rescue schema. Panels B and C show enumeration of FITC CAR T cells in the blood after rescue.
  • FIG. 54 shows the characterization of circulating CAR T cells in mouse blood after rescue.
  • FIG. 55A shows a rescue schema. Panels B and C show enumeration of CAR T cells in the blood after rescue. (1) Control [No NaFL]; (2) 0.06 umol/kg NaFL; (3) 0.6 umol/kg NAFL; (4) 6 umol.kg NaFL.
  • FIG. 56 shows tumor burden in EC 17 treated and non-treated animals.
  • FIG. 57 summarizes the estimated numbers of tumor masses and total tumor weights in all groups examined.
  • FIG. 58 A and 58B show the characterization of circulating tumor cells.
  • FIG. 59A and 59B show the characterization of circulating tumor cells.
  • FIG. 60A and 60B show the percent of whole blood that is CAR T cells upon EC 17 injection.
  • FIG. 61 A and 6 IB show the persistence of blood-borne CAR T cells post infusion of EC 17 with and without rescue and the phenotype post infusion of EC 17.
  • FIG. 62A and 62B show that CAR T cells localized in metastatic tumor lesions, not adjacent healthy tissues, when EC17 is injected.
  • FIG. 63 shows the design and characterization of an anti-fluorescein CAR T cell and fluorescein-folate bridge.
  • A Structure of fluorescein-folate (FITC-folate).
  • C Transduction efficiency of CAR T cells evaluated by flow cytometry.
  • FIG. 64 shows the demonstration that FITC-folate bridge mediates anti- fluorescein CAR T cell engagement with folate receptor-expressing cancer cells (KB cells).
  • A Demonstration that FR is expressed on KB cells. Grey histogram: KB cells without staining; Black histogram: KB cells labeled with ⁇ FITC-folate in the presence of excess (10 ⁇ ) free folate as competitor; Open histogram: KB cells labeled with ⁇ FITC-folate.
  • B Cytotoxicity of CAR T cells towards KB cells upon addition of correct FITC-folate ( ⁇ ) but not mismatched FITC-DUPA (lOOnM) or no (PBS) bridge.
  • C Impact of effector: target cell ratio on CAR T cell lysis of KB cells in presence of FITC- folate, FITC-DUPA, or no bridge.
  • D IFNy production is induced by addition of FITC- folate (lOOnM) but not FITC-DUPA (lOOnM).
  • E Proliferation of anti-fluorescein CAR T cells is induced by FITC-folate but not FITC-DUPA.
  • F Expression of activation marker (CD69) on anti-fluorescein CAR T cells occurs only upon addition of correct bridge.
  • FIG. 65 shows the dependence of CRS on presence of anti-fluorescein CAR T cells, folate receptor positive cancer cells (MDA-MB-231 cells) and FITC-folate in vivo.
  • A Bodyweight change (%) determined 4 days after anti-fluorescein CAR T cell (5x106) infusion into either tumor-free or tumor-bearing mice in the presence or absence of FITC- folate (500nmole/kg administered on days 1 and 2). ** P ⁇ 0.01 by one-way ANOVA test.
  • B Effect of CAR T cell number on bodyweight change (%) on day 4 in tumor-bearing mice after administration of either PBS or 500 nmole/kg FrTC-folate on days 1 and 2.
  • FIG. 66 shows the control of CRS intensity by interruption of bridge administration.
  • A Analysis of body weight change ( ) as a measure of CRS intensity after administration of a high dose of anti-fluorescein CAR T cells (15x106) in the either absence (PBS) or presence of FITC-folate (500nmole/kg administered on days 1, and 2, and alternate days thereafter). In the interrupted dosing regimen, the continuous dosing schedule was followed except FITC-folate injections were omitted on days 4 and 6.
  • B Analysis of IFNy levels in mouse plasma on day 6 using the dosing regimens described in part A.
  • C Analysis of IFNy levels in mouse plasma on day 6 using the dosing regimens described in part A.
  • FIG. 67 shows the effect of blockade of bridge via competition with free folate or free fluorescein on CAR T cell-mediated cytotoxicity.
  • A Measurement of body weight change ( ) after administration of anti-fluorescein CAR T cells (15x106) in the absence (PBS) or presence of FITC-folate (500nmole/kg administered on days 1, and 2, and alternate days thereafter). For competition studies, 100-fold excess folate was co-injected on days 4 and 6. **** P ⁇ 0.0001.
  • B Analysis on day 6 of IFNy levels in plasma of above treatment groups. ** P ⁇ 0.005.
  • FIG. 68 shows the effect of bridge concentration on the regulation of anti- fluorescein CAR T cell cytokine release and anti-tumor activity in vitro and in vivo.
  • B IFNy release from cells described in part A.
  • C The level of IFNy in the plasma of
  • FIG. 69 shows the prevention of CRS by gradual escalation of bridge dose or decrease in bridge dosing frequency.
  • FIG. 70 Panel A shows a dose escalation schema. Panels B-C, show the effect of EC 17 dose escalation on the anti-tumor activity and the toxicity (body weight changes) of CAR-T therapy.
  • FIG. 71 Panel A shows a scheme for testing whether tumor size correlates with body weight changes and IL-6 release during CAR-T/EC17 therapy.
  • Panels B-C show the results for body weight change and IL-6 levels, respectively.
  • FIG. 72 Panel A shows a scheme for testing whether CAR-T/EC17 therapy is effective in an osteosarcoma model.
  • Panel B shows the tumor size results.
  • FIG. 73 shows body weight changes for the tests described for FIG. 72.
  • FIG. 74 Panels A-F show that HOS cancer cells express the FR-a.
  • FIG. 75 shows a scheme for testing whether cytokines are produced in response to CAR-T/EC17 therapy and whether NaFL rescues the mice from CRS.
  • FIGS. 76, Panels A-E show reduction of mouse cytokine production by 60 umol/kg NaFL 7 hours post NaFL rescue.
  • FIGS. 77, Panels A-c show reduction of mouse cytokine production by 60 umol/kg NaFL 27 hours post NaFL rescue.
  • FIG. 78 shows a scheme for testing reduction of mouse cytokine production in response to CAR-T/EC17 therapy by various concentrations of NaFL.
  • FIG. 79 shows reduction of MCP-1 in response to CAR-T/EC17 therapy by NaFL rescue.
  • FIG. 80 shows reduction of IL-6 in response to CAR-T/EC17 therapy by
  • FIG. 81 shows reduction of IL-10 in response to CAR-T/EC17 therapy by
  • FIG. 82 Panel A shows a scheme for testing whether MCP- 1 production in response to CAR-T/EC17 therapy correlates with CAR-T cell number.
  • Panel B shows that MCP-1 production in response to CAR-T/EC17 therapy correlates with CAR-T cell number.
  • a or “an” may mean one or more.
  • “about” in reference to a numeric value including, for example, whole numbers, fractions, and percentages, generally refers to a range of numerical values (e.g., +/- 5 % to 10% of the recited value) that one of ordinary skill in the art would consider equivalent to the recited value (e.g., having the same function or result).
  • treat refers to both therapeutic treatment and prophylactic or preventative treatment.
  • the terms “ameliorate,” “ameliorating,” “amelioration,” or “ameliorated” in reference to cancer can mean reducing the symptoms of the cancer, reducing the size of a tumor, completely or partially removing the tumor (e.g., a complete or partial response), causing stable disease, preventing progression of the cancer (e.g., progression free survival), or any other effect on the cancer that would be considered by a physician to be a therapeutic, prophylactic, or preventative treatment of the cancer.
  • administer means all means of introducing the compound, or pharmaceutically acceptable salt thereof, or CAR T cell composition described herein to the patient, including, but not limited to, oral, intravenous, intramuscular, subcutaneous, and transdermal.
  • off-target toxicity means organ damage or a reduction in the patient's weight that is unacceptable to the physician treating the patient, or any other effect on the patient that is unacceptable to the physician treating the patient, for example, B cell aplasia, a fever, a drop in blood pressure, or pulmonary edema.
  • transduction and “transfection” are used equivalently and the terms mean introducing a nucleic acid into a cell by any artificial method, including viral and non- viral methods.
  • a small molecule ligand linked to a targeting moiety by a linker is used as a bridge between a cancer and CAR T cells (i.e, T cells expressing a chimeric antigen receptor).
  • the bridge directs the CAR T cells to the cancer for amelioration of the cancer.
  • the "small molecule ligand” can be a folate, a CAIX ligand, DUPA, an NK-1R ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, or a CCK2R ligand, each of which is a small molecule ligand that binds specifically to a cancer cell type (i.e., the receptor for each of these ligands is overexpressed on cancers compared to normal tissues).
  • the "targeting moiety" linked to the small molecule ligand binds to the recognition region of the genetically engineered CAR expressed by CAR T cells.
  • the recognition region of the CAR e.g., a single chain fragment variable region (scFv) of an antibody, an Fab, Fv, Fc, or (Fab')2 fragment, and the like
  • the small molecule ligand linked to a targeting moiety by a linker acts as a bridge between the cancer and the CAR T cells directing the CAR T cells to the cancer for amelioration of the cancer.
  • the bridge between the cancer and the CAR T cells can be any of the conjugates shown in the Examples.
  • the bridge is a small organic molecule so clearance from the bloodstream can be rapidly achieved (e.g., about 20 minutes or less).
  • the CAR T cell response can be targeted to only those cancer cells expressing a receptor for the small molecule ligand portion of the 'bridge,' thereby reducing off-target toxicity to normal tissues.
  • this system can be 'universal' because one type of CAR T cell construct can be used to target a wide variety of cancers using different 'bridges'.
  • the targeting moiety recognized by the CAR T cell may remain constant so that one type of CAR T cell construct can be used, while the small molecule ligand that binds to the cancer can be altered to allow targeting of a wide variety of cancers.
  • the small molecule ligand linked to a targeting moiety by a linker is referred to as a "compound.”
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise the CAR directed to the targeting moiety.
  • the ligand is selected from the group consisting of a folate, DUPA, an NK-IR ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • any one of clauses 1 to 26 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphoma,
  • T cell toxicity to the cancer occurs.
  • the first dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non- transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non-transformed T cells, and about 1: 1 of the CAR T cells to the non- transformed T cells.
  • the second dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non- transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non-transformed T cells, and about 1: 1 of the CAR T cells to the non- transformed T cells.
  • the first dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio of from about 1:1 to about 1:5 of the CAR T cells to the non-transformed T cells.
  • the second dose of the CAR T cell composition comprises a mixture of the CAR T cells and non- transformed T cells in a ratio of from about 1:1 to 1:5 of the CAR T cells to the non- transformed T cells.
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • CAR T cell composition comprises CAR T cells, wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells.
  • ligand is selected from the group consisting of a folate, DUPA, an NK- IR ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • any one of clauses 56 to 81 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphom
  • CAR has a recognition region and the recognition region of the CAR is a single chain fragment variable (scFv) region of an anti-FITC antibody.
  • scFv single chain fragment variable
  • a compound or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker;
  • CAR T cell composition comprises CAR T cells and wherein the CAR T cells comprise a CAR directed to the targeting moiety;
  • a conjugate comprising a folate wherein the conjugate comprising a folate does not comprise a targeting moiety, or an agent that inhibits activation of the CAR T cells.
  • step iii comprises administering a folate.
  • step iii comprises administering folic acid or leucovorin.
  • step iii comprises administering the conjugate comprising a folate.
  • Q is selected from the group consisting of C and CH;
  • X 2 and X 3 are each independently selected from the group consisting of oxygen, sulfur, -C(Z)-, -C(Z)0-, -OC(Z)-, -N(R 4b )-, -C(Z)N(R 4b )-, -N(R 4b )C(Z)-,
  • R 1 is selected-from the group consisting of hydrogen, halo, d-C 12 alkyl, and
  • R 2 , R 3 , R 4 , R 4a , R 4b , R 5 , R 5b , R 6b , and R 7b are each independently selected from the group consisting of hydrogen, halo, Ci-C 12 alkyl, Ci-C 12 alkoxy, Ci-Ci 2 alkanoyl, Ci-C 12 alkenyl, Ci-C 12 alkynyl, (Ci-Ci 2 alkoxy)carbonyl, and (Ci-C 12 alkylamino)carbonyl;
  • R 6 and R 7 are each independently selected from the group consisting of hydrogen, halo, Ci-Ci 2 alkyl, and Ci-Ci 2 alkoxy; or, R 6 and R 7 are taken together to form a carbonyl group;
  • R 6a and R 7a are each independently selected from the group consisting of hydrogen, halo, Ci-Ci 2 alkyl, and Ci-Ci 2 alkoxy; or R 6a and R 7a are taken together to form a carbonyl group;
  • p, r, s, and t are each independently either 0 or 1;
  • * represents an optional covalent bond to the rest of the conjugate, if any additional chemical moieties are part of the folate.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein NHS -fluorescein
  • pentafluorophenyl ester tetrafluorophenyl ester
  • a knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an inte ⁇ ⁇ er from 0 to 200.
  • n is an integer from 0 to 150.
  • n is an integer from 0 to 110.
  • n is an integer from 0 to 20.
  • n is an integer from 15 to 20.
  • n is an integer from 15 to 110.
  • any one of clauses 108 to 134 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lymphom
  • CAR T cell composition are administered. 147.
  • T cell toxicity to the cancer occurs.
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • T cells comprise a polypeptide comprising SEQ ID NO:2.
  • the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non-transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non- transformed T cells, and about 1:1 of the CAR T cells to the non-transformed T cells.
  • the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non-transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non-transformed T cells, about 1:2 of the CAR T cells to the non- transformed T cells, and about 1:1 of the CAR T cells to the non-transformed T cells.
  • the CAR T cell composition comprises a mixture
  • the CAR T cell composition comprises a mixture of the CAR T cells and non-transformed T cells in a ratio of from about 1:1 to about 1:5 of the CAR T cells to the non- transformed T cells.
  • T cell composition comprises a mixture comprising about 10 million of the CAR T cells and about 40 million of the non-transformed T cells.
  • the agent that inhibits activation of the CAR T cells is selected from the group consisting of a lymphocyte-specific protein tyrosine kinase inhibitor, a PI3 kinase inhibitor, an inhibitor of an IL-2 inducible T cell kinase, a JAK inhibitor, a BTK inhibitor, EC2319, and an agent that blocks CAR T cell binding to the compound, or the pharmaceutically acceptable salt thereof, but does not bind to the cancer.
  • the dose of the CAR T cells administered to the patient in the CAR T cell composition is selected from the group consisting of about 1 million, about 2 million, about 3 million, about 4 million, about 5 million, about 6 million, about 7 million, about 8 million, about 9 million, about 10 million, about 11 million, about 12 million, about 12.5 million, about 13 million, about 14 million, and about 15 million of the CAR T cells.
  • fluoresceinamine FITC
  • sodium fluorescein sodium fluorescein
  • a method of treatment of a cancer comprising
  • a compound, or a pharmaceutically acceptable salt thereof wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker, and wherein the compound, or the pharmaceutically acceptable salt thereof, is at a dose of about 10 nmoles/kg of body weight of the patient to about 2500 nmoles/kg of body weight of the patient;
  • a CAR T cell composition comprising CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety, and wherein the CAR T cells are at a dose of about 1 million of the CAR T cells to about 15 million of the CAR T cells.
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • the targeting moiety is FITC.
  • the linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200.
  • any one of clauses 183 to 201 wherein the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic leukemia, acute leukemia, acute myelocytic leukemia, lymphocytic lympho
  • T cells comprise a nucleic acid comprising SEQ ID NO: l.
  • a method of treatment of a cancer comprising
  • ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an NKG2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • FITC fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester a knottin
  • a centyrin and a DARPin.
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula
  • n is an integer from 0 to 200. 223.
  • the linker comprises PEG and the targeting moiety is FITC, or a pharmaceutically acceptable salt thereof.
  • any one of clauses 215 to 232 wherein the administration is by intravenous administration.
  • the cancer is selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head, cancer of the neck, cutaneous melanoma, intraocular melanoma uterine cancer, ovarian cancer, endometrial cancer, rectal cancer, stomach cancer, colon cancer, breast cancer, triple negative breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, non-small cell lung cancer, cancer of the adrenal gland, sarcoma of soft tissue, osteosarcoma, cancer of the urethra, prostate cancer, chronic
  • T cell toxicity to the cancer occurs.
  • 240 The method of any one of clauses 215 to 238 wherein off-target tissue toxicity does not occur in the patient and wherein CAR T cell toxicity to the cancer occurs.
  • T cell composition further comprises non-transformed T cells.
  • the CAR T cell composition further comprises non-transformed T cells in a ratio selected from about 1:5 of the CAR T cells to the non-transformed T cells, about 1:4 of the CAR T cells to the non-transformed T cells, about 1:3 of the CAR T cells to the non- transformed T cells, about 1:2 of the CAR T cells to the non-transformed T cells, and about 1:1 of the CAR T cells to the non-transformed T cells.
  • a method of treatment of a cancer comprising i) administering to a patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker and wherein the compound, or the pharmaceutically acceptable salt thereof, is administered once weekly to the patient; and
  • CAR T cells wherein the CAR T cells comprise a CAR directed to the targeting moiety.
  • the ligand is selected from the group consisting of a folate, DUPA, an NK-1R ligand, a CAIX ligand, a ligand of gamma glutamyl transpeptidase, an N G2D ligand, and a CCK2R ligand.
  • the targeting moiety is selected from the group consisting of 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS -fluorescein, pentafluorophenyl ester, tetrafluorophenyl ester, a knottin, a centyrin, and a DARPin.
  • DNP 2,4-dinitrophenol
  • TNP 2,4,6-trinitrophenol
  • biotin digoxigenin
  • fluorescein fluorescein isothiocyanate
  • NHS -fluorescein pentafluorophenyl ester
  • tetrafluorophenyl ester tetrafluorophenyl ester
  • knottin a centyrin
  • DARPin DARPin
  • linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, pluronic F-127, or a combination thereof.
  • L represents the linker
  • T represents the targeting moiety
  • L comprises a structure having the formula

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JP2019547107A JP7178355B2 (ja) 2017-02-28 2018-02-28 Ｃａｒ ｔ細胞療法のための組成物および方法
CN201880028009.XA CN110582288B (zh) 2017-02-28 2018-02-28 用于car t细胞疗法的组合物和方法
ES18761400T ES3010559T3 (en) 2017-02-28 2018-02-28 Compositions and methods for car t cell therapy
US16/489,455 US11850262B2 (en) 2017-02-28 2018-02-28 Compositions and methods for CAR T cell therapy
US16/921,400 US11759480B2 (en) 2017-02-28 2020-07-06 Compositions and methods for CAR T cell therapy
JP2022181982A JP7585280B2 (ja) 2017-02-28 2022-11-14 Ｃａｒ ｔ細胞療法のための組成物および方法
US18/494,613 US20240165159A1 (en) 2017-02-28 2023-10-25 Compositions and methods for car t cell therapy
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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019144095A1 (en) * 2018-01-22 2019-07-25 Seattle Children's Hospital (dba Seattle Children's Research Institute) Methods of use for car t cells
EP3439675A4 (en) * 2016-04-08 2019-12-18 Purdue Research Foundation METHOD AND COMPOSITIONS FOR CAR-T CELL THERAPY
WO2020185917A1 (en) * 2019-03-13 2020-09-17 Seattle Children's Hospital (dba Seattle Children's Research Institute) Sodium fluorescein as a reversal agent for an anti-fluorescein car t cells and fluorescein-phospholipid-ethers or profluorescein-phospholipid-ethers
EP3672615A4 (en) * 2017-08-22 2021-04-21 Purdue Research Foundation FBSA-BASED THERAPEUTIC AND RADIO IMAGING CONJUGATES AGAINST CARBOAN HYDRASE-POSITIVE CANCER TYPES
EP3755366A4 (en) * 2018-02-23 2021-12-29 Endocyte, Inc. Sequencing method for car t cell therapy
US11225520B2 (en) 2016-02-16 2022-01-18 Dana-Farber Cancer Institute, Inc. Immunotherapy compositions and methods
US11649288B2 (en) 2017-02-07 2023-05-16 Seattle Children's Hospital Phospholipid ether (PLE) CAR T cell tumor targeting (CTCT) agents
US11759480B2 (en) 2017-02-28 2023-09-19 Endocyte, Inc. Compositions and methods for CAR T cell therapy
EP4382119A1 (en) 2022-12-09 2024-06-12 AvenCell Europe GmbH A kit for use in the treatment of hematological cancer
WO2024121297A1 (en) 2022-12-09 2024-06-13 Avencell Europe Gmbh A kit for use in the treatment of hematological cancer
US12150981B2 (en) 2012-12-20 2024-11-26 Purdue Research Foundation Chimeric antigen receptor-expressing T cells as anti-cancer therapeutics
US12312416B2 (en) 2018-02-06 2025-05-27 Seattle Children's Hospital Fluorescein-specific cars exhibiting optimal t cell function against FL-PLE labelled tumors
US12466869B2 (en) 2018-06-28 2025-11-11 Dana-Farber Cancer Institute, Inc. Targeting of multiple antigens with multiplex CAR T cells in solid and liquid malignancies

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112020020887A2 (pt) 2018-04-12 2021-04-06 Umoja Biopharma, Inc Vetores virais e linhagens celulares de empacotamento
CA3169960A1 (en) * 2020-02-04 2021-08-12 Seattle Children's Hospital (dba Seattle Children's Research Institute) Anti-dinitrophenol chimeric antigen receptors
CN119137261A (zh) 2021-12-17 2024-12-13 优莫佳生物制药股份有限公司 细胞毒性先天淋巴样细胞及其用途
AU2023272490A1 (en) 2022-05-17 2024-12-12 Umoja Biopharma, Inc. Manufacturing viral particles
JP2025519138A (ja) * 2022-05-26 2025-06-24 パーデュー・リサーチ・ファウンデーション 低分子薬物コンジュゲートおよびｃａｒ発現細胞傷害性リンパ球の組合せならびに使用の方法
IL317466A (en) 2022-06-09 2025-02-01 Umoja Biopharma Inc Compounds and methods for NK cell differentiation
KR20250022800A (ko) 2022-06-10 2025-02-17 우모자 바이오파마 인코포레이티드 조작된 줄기 세포 및 그의 용도
CN114835723B (zh) * 2022-07-01 2022-09-16 戴格普瑞生物科技(苏州)有限公司 Psma荧光分子探针、制备方法及试剂盒
CN119923463A (zh) 2022-07-27 2025-05-02 优莫佳生物制药股份有限公司 在悬浮培养中分化干细胞
TW202434735A (zh) 2022-11-04 2024-09-01 美商烏莫賈生物製藥股份有限公司 展示黏著分子融合的顆粒
KR20250120449A (ko) 2022-11-04 2025-08-08 우모자 바이오파마 인코포레이티드 폴리뉴클레오티드 구축물 및 관련 바이러스 벡터 및 방법
WO2025129084A1 (en) 2023-12-13 2025-06-19 Umoja Biopharma, Inc. Engineered induced stem cell derived myeloid cells and methods of differentiating and using same
WO2025231174A1 (en) 2024-04-30 2025-11-06 Umoja Biopharma, Inc. Manufacturing viral particles

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014100615A1 (en) 2012-12-20 2014-06-26 Purdue Research Foundation Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics
WO2016201300A1 (en) * 2015-06-12 2016-12-15 Immunomedics, Inc. Disease therapy with chimeric antigen receptor (car) constructs and t cells (car-t) or nk cells (car-nk) expressing car constructs
WO2017177149A2 (en) * 2016-04-08 2017-10-12 Purdue Research Foundation Methods and compositions for car t cell therapy

Family Cites Families (394)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0211047B1 (en) 1985-01-28 1994-02-02 Xoma Corporation Arab promoters and method of producing polypeptides, includinn cecropins, by microbiological techniques
US4690915A (en) 1985-08-08 1987-09-01 The United States Of America As Represented By The Department Of Health And Human Services Adoptive immunotherapy as a treatment modality in humans
IN165717B (enExample) 1986-08-07 1989-12-23 Battelle Memorial Institute
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US5202238A (en) 1987-10-27 1993-04-13 Oncogen Production of chimeric antibodies by homologous recombination
US6004781A (en) 1988-01-22 1999-12-21 The General Hospital Corporation Nucleic acid encoding Ig-CD4 fusion proteins
US5906936A (en) 1988-05-04 1999-05-25 Yeda Research And Development Co. Ltd. Endowing lymphocytes with antibody specificity
IL86278A (en) 1988-05-04 2003-06-24 Yeda Res & Dev Endowing cells with antibody specificity using chimeric t cell receptor
US5225538A (en) 1989-02-23 1993-07-06 Genentech, Inc. Lymphocyte homing receptor/immunoglobulin fusion proteins
US5116964A (en) 1989-02-23 1992-05-26 Genentech, Inc. Hybrid immunoglobulins
US6406697B1 (en) 1989-02-23 2002-06-18 Genentech, Inc. Hybrid immunoglobulins
US5216132A (en) 1990-01-12 1993-06-01 Protein Design Labs, Inc. Soluble t-cell antigen receptor chimeric antigens
US20020004052A1 (en) 1990-05-08 2002-01-10 David Berd Composition comprising a tumor cell extract and method of using the composition
US5914109A (en) 1990-06-15 1999-06-22 New York University Heterohybridomas producing human monoclonal antibodies to HIV-1
US6407221B1 (en) 1990-12-14 2002-06-18 Cell Genesys, Inc. Chimeric chains for receptor-associated signal transduction pathways
US6319494B1 (en) 1990-12-14 2001-11-20 Cell Genesys, Inc. Chimeric chains for receptor-associated signal transduction pathways
AU643109B2 (en) 1990-12-14 1993-11-04 Cell Genesys, Inc. Chimeric chains for receptor-associated signal transduction pathways
US20020111474A1 (en) 1990-12-14 2002-08-15 Capon Daniel J. Chimeric chains for receptor-associated signal transduction pathways
US5851828A (en) 1991-03-07 1998-12-22 The General Hospital Corporation Targeted cytolysis of HIV-infected cells by chimeric CD4 receptor-bearing cells
US6753162B1 (en) 1991-03-07 2004-06-22 The General Hospital Corporation Targeted cytolysis of HIV-infected cells by chimeric CD4 receptor-bearing cells
US5912170A (en) 1991-03-07 1999-06-15 The General Hospital Corporation Redirection of cellular immunity by protein-tyrosine kinase chimeras
IL101147A (en) 1991-03-07 2004-06-20 Gen Hospital Corp Redirection of cellular immunity by receptor chimeras
US7049136B2 (en) 1991-03-07 2006-05-23 The General Hospital Corporation Redirection of cellular immunity by receptor chimeras
US5843728A (en) 1991-03-07 1998-12-01 The General Hospital Corporation Redirection of cellular immunity by receptor chimeras
US6004811A (en) 1991-03-07 1999-12-21 The Massachussetts General Hospital Redirection of cellular immunity by protein tyrosine kinase chimeras
WO1992015671A1 (en) 1991-03-08 1992-09-17 Cytomed, Inc. Soluble cd28 proteins and methods of treatment therewith
US6582959B2 (en) 1991-03-29 2003-06-24 Genentech, Inc. Antibodies to vascular endothelial cell growth factor
ATE194494T1 (de) 1991-10-21 2000-07-15 Cell Genesys Inc Kombinierte zelluläre und immunsuppressive therapien
US8211422B2 (en) 1992-03-18 2012-07-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric receptor genes and cells transformed therewith
IL104570A0 (en) 1992-03-18 1993-05-13 Yeda Res & Dev Chimeric genes and cells transformed therewith
US5372930A (en) 1992-09-16 1994-12-13 The United States Of America As Represented By The Secretary Of The Navy Sensor for ultra-low concentration molecular recognition
US6953668B1 (en) 1992-11-05 2005-10-11 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen
US7105159B1 (en) 1992-11-05 2006-09-12 Sloan-Kettering Institute For Cancer Research Antibodies to prostate-specific membrane antigen
EP1757694A3 (en) 1992-11-05 2008-02-27 Sloan Kettering Institute For Cancer Research Prostate-specific membrane antigen
US5861156A (en) 1993-01-08 1999-01-19 Creative Biomolecules Methods of delivering agents to target cells
AU695869B2 (en) 1993-04-06 1998-08-27 Fred Hutchinson Cancer Research Center Chimeric cytokine receptors in lymphocytes
US6051427A (en) 1993-06-11 2000-04-18 Cell Genesys, Inc. Method for production of high titer virus and high efficiency retroviral mediated transduction of mammalian cells
US5834256A (en) 1993-06-11 1998-11-10 Cell Genesys, Inc. Method for production of high titer virus and high efficiency retroviral mediated transduction of mammalian cells
US5525503A (en) 1993-09-28 1996-06-11 Dana-Farber Cancer Institute, Inc. Signal transduction via CD28
US5935818A (en) 1995-02-24 1999-08-10 Sloan-Kettering Institute For Cancer Research Isolated nucleic acid molecule encoding alternatively spliced prostate-specific membrane antigen and uses thereof
DE69528894T2 (de) 1994-05-02 2003-03-27 Bernd Groner Bifunktionelles protein, herstellung und verwendung
US7354587B1 (en) 1994-07-06 2008-04-08 Immunomedics, Inc. Use of immunoconjugates to enhance the efficacy of multi-stage cascade boosting vaccines
US5798100A (en) 1994-07-06 1998-08-25 Immunomedics, Inc. Multi-stage cascade boosting vaccine
US5716614A (en) 1994-08-05 1998-02-10 Molecular/Structural Biotechnologies, Inc. Method for delivering active agents to mammalian brains in a complex with eicosapentaenoic acid or docosahexaenoic acid-conjugated polycationic carrier
WO1996013584A1 (en) 1994-11-01 1996-05-09 Targeted Genetics Corporation Chimeric receptors for the generation of selectively-activatable th-independent cytotoxic t cells
US5837544A (en) 1995-02-02 1998-11-17 Cell Genesys, Inc. Method of inducing a cell to proliferate using a chimeric receptor comprising janus kinase
US5712149A (en) 1995-02-03 1998-01-27 Cell Genesys, Inc. Chimeric receptor molecules for delivery of co-stimulatory signals
US6103521A (en) 1995-02-06 2000-08-15 Cell Genesys, Inc. Multispecific chimeric receptors
US7037647B1 (en) 1995-02-24 2006-05-02 Sloan-Kettering Institute For Cancer Research Prostate-specific membrane antigen and uses thereof
US5830755A (en) 1995-03-27 1998-11-03 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services T-cell receptors and their use in therapeutic and diagnostic methods
WO1997004752A1 (en) 1995-07-26 1997-02-13 Duramed Pharmaceuticals, Inc. Pharmaceutical compositions of conjugated estrogens and methods for their use
GB9526131D0 (en) 1995-12-21 1996-02-21 Celltech Therapeutics Ltd Recombinant chimeric receptors
WO1997034634A1 (en) 1996-03-20 1997-09-25 Sloan-Kettering Institute For Cancer Research Single chain fv constructs of anti-ganglioside gd2 antibodies
US6261787B1 (en) 1996-06-03 2001-07-17 Case Western Reserve University Bifunctional molecules for delivery of therapeutics
US5969102A (en) 1997-03-03 1999-10-19 St. Jude Children's Research Hospital Lymphocyte surface receptor that binds CAML, nucleic acids encoding the same and methods of use thereof
US20020018783A1 (en) 1997-03-20 2002-02-14 Michel Sadelain Fusion proteins of a single chain antibody and cd28 and uses thereof
JP2002504827A (ja) 1997-06-11 2002-02-12 ニューヨーク ユニバーシティ プレニルシステインカルボキシルメチルトランスフェラーゼ、これをコード化するｄｎａ、およびその阻害剤のためのスクリーニング方法
US6759243B2 (en) 1998-01-20 2004-07-06 Board Of Trustees Of The University Of Illinois High affinity TCR proteins and methods
US20090011984A1 (en) 1998-02-23 2009-01-08 Seppo Yla-Herttuala Biotin-binding receptor molecules
GB9809951D0 (en) 1998-05-08 1998-07-08 Univ Cambridge Tech Binding molecules
DK1066380T3 (da) 1998-05-19 2002-01-28 Avidex Ltd Opløselig T-cellereceptor
WO2000014257A1 (en) 1998-09-04 2000-03-16 Sloan-Kettering Institute For Cancer Research Fusion receptors specific for prostate-specific membrane antigen and uses thereof
AU2472400A (en) 1998-10-20 2000-05-08 City Of Hope CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies
US6534633B1 (en) 1998-10-21 2003-03-18 Altor Bioscience Corporation Polyspecific binding molecules and uses thereof
US7217421B1 (en) 1998-11-03 2007-05-15 Cell Genesys, Inc. Cancer-associated antigens and methods of their identification and use
AU3389700A (en) 1999-03-01 2000-09-21 Cell Genesys, Inc. Anti-neoplastic compositions and uses thereof
JP2002541845A (ja) 1999-04-16 2002-12-10 セルテック セラピューティックス リミテッド 合成膜貫通成分
US6699972B1 (en) 1999-06-25 2004-03-02 Academia Sinica Chimeric protein and method of controlling tumor growth using the protein
JP4723782B2 (ja) 2000-01-03 2011-07-13 ティーアール アソシエイツ，エル．エル．シー． 新規なキメラ蛋白質及び該蛋白質の使用方法
US7572891B2 (en) 2000-02-14 2009-08-11 The Regents Of The University Of California Kidney-specific tumor vaccine directed against kidney tumor antigen G-250
US6770749B2 (en) 2000-02-22 2004-08-03 City Of Hope P53-specific T cell receptor for adoptive immunotherapy
EP1267918A4 (en) 2000-03-31 2007-06-27 Purdue Research Foundation METHOD OF TREATMENT USING LIGAND-IMMUNOGENE CONJUGATES
WO2001091625A2 (en) 2000-04-21 2001-12-06 Rutgers, The State University Of New Jersey Methods and compositions for the diagnosis of schizophrenia
US6524572B1 (en) 2000-06-26 2003-02-25 Rainbow Therapeutic Company Targeting recombinant virus with a bispecific fusion protein ligand in coupling with an antibody to cells for gene therapy
CA2417570C (en) 2000-07-31 2010-12-07 Kyogo Itoh Tumor-specific t cell activation by peptide antigens
US7666424B2 (en) 2001-10-17 2010-02-23 Sloan-Kettering Institute For Cancer Research Methods of preparing and using single chain anti-tumor antibodies
EP1334188B1 (en) 2000-11-07 2006-08-30 City of Hope Cd19-specific redirected immune cells
US20020132983A1 (en) 2000-11-30 2002-09-19 Junghans Richard P. Antibodies as chimeric effector cell receptors against tumor antigens
US7723111B2 (en) 2001-03-09 2010-05-25 The United States Of America As Represented By The Department Of Health And Human Services Activated dual specificity lymphocytes and their methods of use
US7070995B2 (en) 2001-04-11 2006-07-04 City Of Hope CE7-specific redirected immune cells
CA2445746C (en) 2001-04-30 2012-09-18 City Of Hope Chimeric immunoreceptor useful in treating human cancers
US20090257994A1 (en) 2001-04-30 2009-10-15 City Of Hope Chimeric immunoreceptor useful in treating human cancers
US7514537B2 (en) 2001-04-30 2009-04-07 City Of Hope Chimeric immunoreceptor useful in treating human gliomas
US20070031438A1 (en) 2001-12-10 2007-02-08 Junghans Richard P Antibodies as chimeric effector cell receptors against tumor antigens
US7939059B2 (en) 2001-12-10 2011-05-10 California Institute Of Technology Method for the generation of antigen-specific lymphocytes
US20030170238A1 (en) 2002-03-07 2003-09-11 Gruenberg Micheal L. Re-activated T-cells for adoptive immunotherapy
US7446190B2 (en) 2002-05-28 2008-11-04 Sloan-Kettering Institute For Cancer Research Nucleic acids encoding chimeric T cell receptors
US7906620B2 (en) 2002-08-16 2011-03-15 Yeda Research And Development Co. Ltd. Tumor associated antigen, peptides thereof, and use of same as anti-tumor vaccines
WO2004021861A2 (en) 2002-09-03 2004-03-18 Vit Lauermann Targeted release
DE10244457A1 (de) 2002-09-24 2004-04-01 Johannes-Gutenberg-Universität Mainz Verfahren zur rationalen Mutagenese von alpha/beta T-Zell Rezeptoren und entsprechend mutierte MDM2-Protein spezifische alpha/beta T-Zell Rezeptoren
AR038085A1 (es) 2002-12-27 2004-12-29 Univ Nac Quilmes Analogos de 1-desamino-8-d-arginina vasopresina
US20050129671A1 (en) 2003-03-11 2005-06-16 City Of Hope Mammalian antigen-presenting T cells and bi-specific T cells
US20060018878A1 (en) 2003-03-11 2006-01-26 City Of Hope Dual antigen specific T cells with trafficking ability
US7348004B2 (en) 2003-05-06 2008-03-25 Syntonix Pharmaceuticals, Inc. Immunoglobulin chimeric monomer-dimer hybrids
TWI353991B (en) 2003-05-06 2011-12-11 Syntonix Pharmaceuticals Inc Immunoglobulin chimeric monomer-dimer hybrids
US7435596B2 (en) 2004-11-04 2008-10-14 St. Jude Children's Research Hospital, Inc. Modified cell line and method for expansion of NK cell
US20130266551A1 (en) 2003-11-05 2013-10-10 St. Jude Children's Research Hospital, Inc. Chimeric receptors with 4-1bb stimulatory signaling domain
US20050113564A1 (en) 2003-11-05 2005-05-26 St. Jude Children's Research Hospital Chimeric receptors with 4-1BB stimulatory signaling domain
US8652484B2 (en) 2004-02-13 2014-02-18 Immunomedics, Inc. Delivery system for cytotoxic drugs by bispecific antibody pretargeting
WO2005079836A1 (en) 2004-02-18 2005-09-01 Wisconsin Alumni Research Foundation Method for treating glaucoma
ATE437657T1 (de) 2004-03-02 2009-08-15 Cellectar Inc Phospholipid-analoga für die behandlung von krebs
US7618817B2 (en) 2004-07-10 2009-11-17 Fox Chase Cancer Center Genetically modified human natural killer cell lines
TWI380996B (zh) 2004-09-17 2013-01-01 Hoffmann La Roche 抗ｏｘ４０ｌ抗體
US7994298B2 (en) 2004-09-24 2011-08-09 Trustees Of Dartmouth College Chimeric NK receptor and methods for treating cancer
US7998736B2 (en) 2004-10-08 2011-08-16 The United States Of America As Represented By The Department Of Health And Human Services Adoptive immunotherapy with enhanced T lymphocyte survival
AU2005335714B2 (en) 2004-11-10 2012-07-26 Macrogenics, Inc. Engineering Fc antibody regions to confer effector function
WO2007044033A2 (en) 2004-12-07 2007-04-19 University Of Pittsburgh Of The Commonwealth System Of Higher Education Therapeutic and diagnostic cloned mhc-unrestricted receptor specific for the muc1 tumor associated antigen
US20070036773A1 (en) 2005-08-09 2007-02-15 City Of Hope Generation and application of universal T cells for B-ALL
EP1979379B1 (en) 2005-12-02 2013-09-18 Dana-Farber Cancer Institute Carbonic anhydrase ix (g250) antibodies and methods of use thereof
US7919079B2 (en) 2006-03-31 2011-04-05 Biosante Pharmaceuticals, Inc. Cancer immunotherapy compositions and methods of use
CN105837690A (zh) 2006-06-12 2016-08-10 新兴产品开发西雅图有限公司 具有效应功能的单链多价结合蛋白
WO2007147901A1 (en) 2006-06-22 2007-12-27 Novo Nordisk A/S Production of bispecific antibodies
US20080051380A1 (en) 2006-08-25 2008-02-28 Auerbach Alan H Methods and compositions for treating cancer
EP1900752A1 (en) 2006-09-15 2008-03-19 DOMPE' pha.r.ma s.p.a. Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma
WO2008045437A2 (en) 2006-10-09 2008-04-17 The General Hospital Corporation Chimeric t-cell receptors and t-cells targeting egfrviii on tumors
US9334330B2 (en) 2006-10-10 2016-05-10 Universite De Nantes Use of monoclonal antibodies specific to the O-acetylated form of GD2 ganglioside for the treatment of certain cancers
JP2010509570A (ja) 2006-11-03 2010-03-25 パーデュー・リサーチ・ファウンデーション エクスビボフローサイトメトリーの方法および装置
CA2667414C (en) 2006-11-13 2015-12-29 Sangamo Biosciences, Inc. Methods and compositions for modification of the human glucocorticoid receptor locus
US20080131415A1 (en) 2006-11-30 2008-06-05 Riddell Stanley R Adoptive transfer of cd8 + t cell clones derived from central memory cells
US8748405B2 (en) 2007-01-26 2014-06-10 City Of Hope Methods and compositions for the treatment of cancer or other diseases
JP5299902B2 (ja) 2007-01-30 2013-09-25 中外製薬株式会社 キメラＦｃγレセプター及び該レセプターを用いたＡＤＣＣ活性測定方法
US20100135974A1 (en) 2007-01-31 2010-06-03 Yeda Research And Development Co. Ltd. Redirected, genetically-engineered t regulatory cells and their use in suppression of autoimmune and inflammatory disease
US8859229B2 (en) 2007-02-02 2014-10-14 Yale University Transient transfection with RNA
US8865169B2 (en) 2007-02-20 2014-10-21 Tufts University Methods and systems for multi-antibody therapies
PT2856876T (pt) 2007-03-30 2018-03-28 Memorial Sloan Kettering Cancer Center Expressão constitutiva de ligantes co-estimulatórios em linfócitos t adotivamente transferidos
EP2177230A4 (en) 2007-08-09 2011-04-27 Daiichi Sankyo Co Ltd IMMUNOLIPOSOM AS INDUCTOR OF APOPTOSIS INTO DEATH DOMAIN-CONTAINING RECEPTOR EXPRESSING CELL
WO2009091826A2 (en) 2008-01-14 2009-07-23 The Board Of Regents Of The University Of Texas System Compositions and methods related to a human cd19-specific chimeric antigen receptor (h-car)
US20110070191A1 (en) 2008-03-19 2011-03-24 Wong Hing C T cell receptor fusions and conjugates and methods of use there of
DK2279253T3 (en) 2008-04-09 2017-02-13 Maxcyte Inc Construction and application of therapeutic compositions of freshly isolated cells
AU2009234277B2 (en) 2008-04-11 2014-12-04 Aptevo Research And Development Llc CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
US20090324630A1 (en) 2008-04-21 2009-12-31 Jensen Michael C Fusion multiviral chimeric antigen
PL3006459T3 (pl) 2008-08-26 2022-01-17 City Of Hope Sposób i kompozycje dla wzmocnionego działania efektorowego komórek t przeciw guzowi nowotworowemu
CN102215844A (zh) 2008-09-17 2011-10-12 恩多塞特公司 抗叶酸剂的叶酸受体结合轭合物
GB2483810B (en) 2008-11-07 2012-09-05 Sequenta Inc Methods for correlating clonotypes with diseases in a population
WO2010059253A2 (en) 2008-11-24 2010-05-27 Massachusets Institute Of Technology Methods and compositions for localized agent delivery
US20110178279A1 (en) 2009-08-03 2011-07-21 Williams John C Development of masked therapeutic antibodies to limit off-target effects: application to anti-egfr antibodies
WO2010132532A1 (en) 2009-05-15 2010-11-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services B cell surface reactive antibodies
US20100322909A1 (en) 2009-06-17 2010-12-23 The University Of Pittsburgh - Of The Commonwealth System Of Higher Education Th1-associated micrornas and their use for tumor immunotherapy
EP2483301A1 (en) 2009-10-01 2012-08-08 The United States Of America, As Represented By The Secretary, Department of Health and Human Services Anti-vascular endothelial growth factor receptor-2 chimeric antigen receptors and use of same for the treatment of cancer
CN102597222B (zh) 2009-10-27 2015-07-15 因缪尼卡姆股份公司 用于增殖抗原特异性t细胞的方法
US9273283B2 (en) 2009-10-29 2016-03-01 The Trustees Of Dartmouth College Method of producing T cell receptor-deficient T cells expressing a chimeric receptor
WO2011059836A2 (en) 2009-10-29 2011-05-19 Trustees Of Dartmouth College T cell receptor-deficient t cell compositions
ES2911246T3 (es) 2009-11-03 2022-05-18 Hope City Receptor del factor de crecimiento epidérmico truncado (EGFRT) para selección de células T transducidas
JP2013512694A (ja) 2009-12-08 2013-04-18 ウィルソン ウォルフ マニュファクチャリング コーポレイション 養子細胞療法のための細胞を培養する方法
US8956860B2 (en) 2009-12-08 2015-02-17 Juan F. Vera Methods of cell culture for adoptive cell therapy
PT2529020T (pt) 2010-01-28 2018-07-30 Childrens Hospital Philadelphia Plataforma de fabrico escalável para purificação de vetor viral e vetores virais assim purificados para utilização na terapia génica
US9133436B2 (en) 2010-02-04 2015-09-15 The Trustees Of The University Of Pennsylvania ICOS critically regulates the expansion and function of inflammatory human Th17 cells
US8551715B2 (en) 2010-02-12 2013-10-08 Oncomed Pharmaceuticals, Inc. Methods for identifying and isolating cells expressing a polypeptide
SA111320200B1 (ar) 2010-02-17 2014-02-16 ديبيوفارم اس ايه مركبات ثنائية الحلقة واستخداماتها كمثبطات c-src/jak مزدوجة
EP3202410B1 (en) 2010-04-14 2020-03-25 Roger Williams Medical Center Methods and compositions for treating hiv
WO2011140170A1 (en) 2010-05-04 2011-11-10 Yeda Research And Development Co. Ltd. Immunotherapy using redirected allogeneic cells
US9089520B2 (en) 2010-05-21 2015-07-28 Baylor College Of Medicine Methods for inducing selective apoptosis
WO2011159847A2 (en) 2010-06-15 2011-12-22 The Regents Of The University Of California Receptor tyrosine kinase-like orphan receptor 1 (ror1) single chain fv antibody fragment conjugates and methods of use thereof
WO2012012695A2 (en) 2010-07-23 2012-01-26 Fred Hutchinson Cancer Research Center A method for the treatment of obesity
DE102010036122A1 (de) 2010-09-01 2012-03-01 Nora Systems Gmbh Bodenbelag
WO2012136231A1 (en) 2010-09-08 2012-10-11 Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus Interleukin 15 as selectable marker for gene transfer in lymphocytes
US9493740B2 (en) 2010-09-08 2016-11-15 Baylor College Of Medicine Immunotherapy of cancer using genetically engineered GD2-specific T cells
US9212229B2 (en) 2010-09-08 2015-12-15 Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus Chimeric antigen receptors with an optimized hinge region
CN103124740B (zh) 2010-09-21 2015-09-02 美国卫生和人力服务部 抗-ssx-2t细胞受体和相关材料及使用方法
CN103154257A (zh) 2010-09-26 2013-06-12 大玉企业有限公司 重组大分子生成方法
US9845362B2 (en) 2010-10-08 2017-12-19 The University Of North Carolina At Charlotte Compositions comprising chimeric antigen receptors, T cells comprising the same, and methods of using the same
WO2012054825A1 (en) 2010-10-22 2012-04-26 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-mage-a3 t cell receptors and related materials and methods of use
CN102827272B (zh) * 2010-11-08 2014-04-02 上海汉升生物科技有限公司 一种叶酸偶联抗体药物及其制备方法与应用
WO2012076059A1 (en) 2010-12-09 2012-06-14 Stichting Het Nederlands Kanker Instituut Immune restricted peptides with increased efficacy
PH12013501201A1 (en) 2010-12-09 2013-07-29 Univ Pennsylvania Use of chimeric antigen receptor-modified t cells to treat cancer
EP2651442B1 (en) 2010-12-14 2020-04-22 University of Maryland, Baltimore Universal anti-tag chimeric antigen receptor-expressing t cells and methods of treating cancer
AU2012207356A1 (en) 2011-01-18 2013-08-01 The Trustees Of The University Of Pennsylvania Compositions and methods for treating cancer
CA2826942C (en) 2011-02-11 2021-08-03 Memorial Sloan-Kettering Cancer Center Hla-restricted, peptide-specific antigen binding proteins
KR101976882B1 (ko) 2011-03-23 2019-05-09 프레드 헛친슨 켄서 리서치 센터 세포 면역요법용 방법 및 조성물
EP2502934B1 (en) 2011-03-24 2018-01-17 Universitätsmedizin der Johannes Gutenberg-Universität Mainz Single chain antigen recognizing constructs (scARCs) stabilized by the introduction of novel disulfide bonds
JP6082997B2 (ja) 2011-04-01 2017-02-22 メモリアル スローン−ケタリング キャンサー センター Ｈｌａ−ａ２により提示されるｗｔ１ペプチドへのｔ細胞受容体様抗体
CN107188969B (zh) 2011-04-08 2021-08-27 美国卫生和人力服务部 抗-表皮生长因子受体变体iii嵌合抗原受体及其用于治疗癌症的用途
US9492529B2 (en) 2011-04-13 2016-11-15 Immunicum Ab Method for priming of T cells
CN103502439B (zh) 2011-04-13 2016-10-12 因缪尼卡姆股份公司 用于抗原特异性t细胞增殖的方法
EP2998320B1 (en) 2011-04-19 2018-07-18 The United States of America, as represented by the Secretary, Department of Health and Human Services Human monoclonal antibodies specific for glypican-3 and use thereof
GB201108236D0 (en) 2011-05-17 2011-06-29 Ucl Business Plc Method
PE20141520A1 (es) 2011-07-29 2014-11-17 Univ Pennsylvania Receptores coestimuladores de cambio
WO2013026839A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use
US9833476B2 (en) 2011-08-31 2017-12-05 The Trustees Of Dartmouth College NKP30 receptor targeted therapeutics
SI2755997T1 (sl) 2011-09-15 2018-11-30 The United States of America, as represented by Secretary, Department of Health and Human Services, Office of Technology Transfer, National Institutes of Health T-celični receptorji, ki prepoznajo HLA-A1- ali HLA-CW7-omejeni mage
US20140255363A1 (en) 2011-09-16 2014-09-11 Baylor College Of Medicine Targeting the tumor microenvironment using manipulated nkt cells
SG11201400527XA (en) 2011-09-16 2014-04-28 Univ Pennsylvania Rna engineered t cells for the treatment of cancer
WO2013044225A1 (en) 2011-09-22 2013-03-28 The Trustees Of The University Of Pennsylvania A universal immune receptor expressed by t cells for the targeting of diverse and multiple antigens
EP2765193B1 (en) 2011-10-07 2017-08-09 Mie University Chimeric antigen receptor
WO2013059593A1 (en) 2011-10-20 2013-04-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-cd22 chimeric antigen receptors
KR101471647B1 (ko) 2011-10-26 2014-12-11 국립암센터 변이 ｃｔｌａ4 유전자 이입 ｔ 세포 및 이를 포함하는 항암 면역치료용 조성물
WO2013063419A2 (en) 2011-10-28 2013-05-02 The Trustees Of The University Of Pennsylvania A fully human, anti-mesothelin specific chimeric immune receptor for redirected mesothelin-expressing cell targeting
US9226936B2 (en) 2011-10-28 2016-01-05 The Wistar of Anatomy and Biology Methods and compositions for enhancing the therapeutic effect of anti-tumor T cells
EP2773651B1 (en) 2011-11-03 2020-12-23 The Trustees of the University of Pennsylvania Isolated b7-h4 specific compositions and methods of use thereof
US20140322216A1 (en) 2011-11-08 2014-10-30 The Trustees Of The University Of Pennsylvania Glypican-3-specific antibody and uses thereof
JP6368243B2 (ja) 2011-11-11 2018-08-08 フレッド ハッチンソン キャンサー リサーチ センター がんのためのサイクリンａ１に標的化されたｔ細胞免疫療法
JP2015500648A (ja) 2011-12-16 2015-01-08 ターゲットジーン バイオテクノロジーズ リミテッド 所定の標的核酸配列を修飾するための組成物及び方法
WO2013093809A1 (en) 2011-12-23 2013-06-27 Pfizer Inc. Engineered antibody constant regions for site-specific conjugation and methods and uses therefor
AU2013211824B2 (en) 2012-01-27 2017-06-01 Gliknik Inc. Fusion proteins comprising IgG2 hinge domains
JP6850528B2 (ja) 2012-02-13 2021-03-31 シアトル チルドレンズ ホスピタル ドゥーイング ビジネス アズ シアトル チルドレンズ リサーチ インスティテュート 二重特異性キメラ抗原受容体およびその治療的使用
MX2014010185A (es) 2012-02-22 2014-11-14 Univ Pennsylvania Uso de dominio de señalizacion cd2 en receptores de antigeno quimericos de segunda generacion.
WO2013126726A1 (en) 2012-02-22 2013-08-29 The Trustees Of The University Of Pennsylvania Double transgenic t cells comprising a car and a tcr and their methods of use
EP2817330B1 (en) 2012-02-22 2020-07-08 The Trustees of the University of Pennsylvania Use of icos-based cars to enhance antitumor activity and car persistence
CA3209571A1 (en) 2012-03-23 2013-09-26 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-mesothelin chimeric antigen receptors
WO2013154760A1 (en) 2012-04-11 2013-10-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting b-cell maturation antigen
US9156915B2 (en) 2012-04-26 2015-10-13 Thomas Jefferson University Anti-GCC antibody molecules
RU2665548C2 (ru) 2012-05-03 2018-08-30 Фред Хатчинсон Кансэр Рисёч Сентер Способ получения клеток, экспрессирующих т-клеточный рецептор
WO2013169691A1 (en) 2012-05-07 2013-11-14 Trustees Of Dartmouth College Anti-b7-h6 antibody, fusion proteins, and methods of using the same
ES2835200T3 (es) 2012-05-22 2021-06-22 Us Health Uso médico de células que comprenden receptores de células T anti-NY-ESO-1
KR101719893B1 (ko) 2012-05-22 2017-03-24 제넨테크, 인크. Ｎ-치환된 벤즈아미드 및 통증의 치료에서 이들의 용도
CA3133545C (en) 2012-05-25 2023-08-08 Cellectis Use of pre t alpha or functional variant thereof for expanding tcr alpha deficient t cells
KR102159773B1 (ko) 2012-06-01 2020-09-28 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 글리피칸-3에 대한 고친화력 단클론 항체 및 이의 용도
KR20150013935A (ko) 2012-06-08 2015-02-05 갓코 호진 긴키 다이가쿠 트랜스포터에 대한 항체 및 이의 용도
JP5863585B2 (ja) 2012-07-11 2016-02-16 三菱電機株式会社 大信号等価回路モデルを用いたトランジスタ特性計算装置
ES2778701T3 (es) 2012-07-13 2020-08-11 The Trustees Of The Univ Of Pennsylvania Center For Technology Transfer Gestión de toxicidad para la actividad antitumoral de CAR
BR112015000310A2 (pt) 2012-07-13 2017-06-27 Univ Pennsylvania conjugado droga-molécula, e, método para inibir o esgotamento do tecido saudável durante a terapia com células t car
CN104583230A (zh) 2012-07-13 2015-04-29 宾夕法尼亚大学董事会 通过共同引入双特异性抗体增强car t细胞的活性
JP6482461B2 (ja) 2012-07-13 2019-03-13 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア 投与に関する形質導入ｔ細胞の適合性の評価方法
CN102775500A (zh) 2012-08-03 2012-11-14 郑骏年 嵌合抗原受体iRGD-scFv(G250)-CD8-CD28-CD137-CD3ζ及其用途
PL2884999T3 (pl) 2012-08-20 2021-07-05 Fred Hutchinson Cancer Research Center Sposób i kompozycje do immunoterapii komórkowej
CA2882753C (en) 2012-08-21 2021-08-24 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Mesothelin domain-specific monoclonal antibodies and use thereof
AU2013312838B2 (en) 2012-09-04 2018-11-29 Cellectis Multi-chain chimeric antigen receptor and uses thereof
US9879065B2 (en) 2012-09-14 2018-01-30 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services T cell receptors recognizing MHC class II-restricted MAGE-A3
AU2013324049B2 (en) 2012-09-27 2017-09-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Mesothelin antibodies and methods for eliciting potent antitumor activity
US9365641B2 (en) 2012-10-01 2016-06-14 The Trustees Of The University Of Pennsylvania Compositions and methods for targeting stromal cells for the treatment of cancer
RU2729401C2 (ru) 2012-10-02 2020-08-06 Мемориал Слоан-Кеттеринг Кэнсер Сентер Композиции и способы для иммунотерапии
WO2014055657A1 (en) 2012-10-05 2014-04-10 The Trustees Of The University Of Pennsylvania Use of a trans-signaling approach in chimeric antigen receptors
WO2014055771A1 (en) 2012-10-05 2014-04-10 The Trustees Of The University Of Pennsylvania Human alpha-folate receptor chimeric antigen receptor
ES2824024T3 (es) 2012-10-10 2021-05-11 Sangamo Therapeutics Inc Compuestos modificadores de células T y usos de los mismos
US20140120136A1 (en) 2012-10-12 2014-05-01 The Babraham Institute Mir-155 enhancement of cd8+ t cell immunity
UY35103A (es) 2012-10-29 2014-05-30 Glaxo Group Ltd Compuestos de cefem 2-sustituidos
AU2013204922B2 (en) 2012-12-20 2015-05-14 Celgene Corporation Chimeric antigen receptors
WO2014099671A1 (en) 2012-12-20 2014-06-26 Bluebird Bio, Inc. Chimeric antigen receptors and immune cells targeting b cell malignancies
SG11201505858VA (en) 2013-01-28 2015-09-29 St Jude Childrens Res Hospital A chimeric receptor with nkg2d specificity for use in cell therapy against cancer and infectious disease
WO2014124143A1 (en) 2013-02-06 2014-08-14 Anthrogenesis Corporation Modified t lymphocytes having improved specificity
JO3529B1 (ar) 2013-02-08 2020-07-05 Amgen Res Munich Gmbh مضاد التصاق خلايا الدم البيض من أجل التخفيف من الاثار السلبية الممكنة الناتجة عن مجالات ارتباط cd3- المحدد
LT2956175T (lt) 2013-02-15 2017-12-11 The Regents Of The University Of California Chimerinis antigeno receptorius ir jo panaudojimo būdai
SG11201505896YA (en) 2013-02-20 2015-09-29 Novartis Ag Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor
EP3744736A1 (en) 2013-02-20 2020-12-02 Novartis AG Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells
US9434935B2 (en) 2013-03-10 2016-09-06 Bellicum Pharmaceuticals, Inc. Modified caspase polypeptides and uses thereof
EP2968552B1 (en) 2013-03-14 2020-03-11 The Scripps Research Institute Targeting agent antibody conjugates and uses thereof
US9499855B2 (en) 2013-03-14 2016-11-22 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
KR20150131218A (ko) 2013-03-14 2015-11-24 벨리쿰 파마슈티컬스, 인크. T 세포 증식의 제어 방법
US9402888B2 (en) 2013-03-14 2016-08-02 The Wistar Institute Of Anatomy And Biology Methods and compositions for treating cancer
US9587237B2 (en) 2013-03-14 2017-03-07 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
US9393268B2 (en) 2013-03-15 2016-07-19 Thomas Jefferson University Cell-based anti-cancer compositions with reduced toxicity and methods of making and using the same
US9561291B2 (en) 2013-03-15 2017-02-07 Imre Kovesdi Methods of targeting T-cells to tumors
EP2970426B1 (en) 2013-03-15 2019-08-28 Michael C. Milone Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy
CN105518018B (zh) 2013-03-15 2020-04-03 细胞基因公司 修饰的t淋巴细胞
US9657105B2 (en) 2013-03-15 2017-05-23 City Of Hope CD123-specific chimeric antigen receptor redirected T cells and methods of their use
US9446105B2 (en) 2013-03-15 2016-09-20 The Trustees Of The University Of Pennsylvania Chimeric antigen receptor specific for folate receptor β
UY35468A (es) 2013-03-16 2014-10-31 Novartis Ag Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19
US9790282B2 (en) 2013-03-25 2017-10-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-CD276 polypeptides, proteins, and chimeric antigen receptors
KR102238226B1 (ko) 2013-05-14 2021-04-09 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 가공된 키메라 항원 수용체 (ｃａｒ) ｔ-세포의 인간 적용
AU2014265331B2 (en) 2013-05-15 2019-12-05 Sangamo Therapeutics, Inc. Methods and compositions for treatment of a genetic condition
WO2014190273A1 (en) 2013-05-24 2014-11-27 Board Of Regents, The University Of Texas System Chimeric antigen receptor-targeting monoclonal antibodies
DK3004337T3 (da) 2013-05-29 2017-11-13 Cellectis Fremgangsmåde til konstruktion af T-celler til immunoterapi ved brug af RNA-guidet Cas nuklease-system
ES2883131T3 (es) 2013-05-29 2021-12-07 Cellectis Métodos para la modificación de células T para inmunoterapia utilizando el sistema de nucleasa CAS guiado por ARN
CA2912172A1 (en) 2013-06-05 2014-12-11 Bellicum Pharmaceuticals, Inc. Methods for inducing partial apoptosis using caspase polypeptides
WO2014200891A1 (en) 2013-06-11 2014-12-18 THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTEMENT OF HEALTH & HUMAN SERVICES Her2-specific monoclonal antibodies and conjugates thereof
BR112015032690B1 (pt) 2013-06-25 2020-03-10 Vaccinex, Inc. Uso de moléculas inibidoras de semaforina-4d em combinação com uma terapia imunomoduladora para inibir o crescimento tumoral e metástase
EP3492094A1 (en) 2013-08-30 2019-06-05 Board of Regents, The University of Texas System Administration of kynurenine depleting enzymes for tumor therapy
WO2015038579A1 (en) 2013-09-11 2015-03-19 Equip, Llc Discrete peg based dyes
US9765142B2 (en) 2013-10-11 2017-09-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services TEM8 antibodies and their use in treatment and detection of tumors
CA2927543C (en) 2013-10-15 2021-07-20 The California Institute For Biomedical Research Peptidic chimeric antigen receptor t cell switches and uses thereof
KR102357968B1 (ko) 2013-10-15 2022-02-03 더 스크립스 리서치 인스티튜트 키메라 항원 수용체 t 세포 스위치 및 이의 용도
US10144770B2 (en) 2013-10-17 2018-12-04 National University Of Singapore Chimeric receptors and uses thereof in immune therapy
AU2014342020C1 (en) 2013-10-31 2019-09-05 Fred Hutchinson Cancer Research Center Modified hematopoietic stem/progenitor and non-T effector cells, and uses thereof
JP2017507917A (ja) 2014-01-14 2017-03-23 セレクティスＣｅｌｌｅｃｔｉｓ 軟骨魚類由来の抗原認識ドメインを使用したキメラ抗原受容体
US9694033B2 (en) 2014-01-24 2017-07-04 The Cleveland Clinic Foundation IL-9 secreting CD8+ Tc9 cells and methods of treating cancer
CN106132423B (zh) 2014-02-14 2020-07-31 贝里坤制药股份有限公司 用诱导型嵌合多肽活化t细胞的方法
CA2939093A1 (en) 2014-02-14 2015-08-20 Immune Design Corp. Immunotherapy of cancer through combination of local and systemic immune stimulation
CN106471004A (zh) 2014-02-28 2017-03-01 麦吉尔大学学术发展皇家学院 作为用于免疫疗法的apc活化剂的tc‑ptp抑制剂
GB201403875D0 (en) 2014-03-05 2014-04-16 Cantargia Ab Novel antibodies and uses thereof
KR101605421B1 (ko) 2014-03-05 2016-03-23 국립암센터 B 세포 림프종 세포를 특이적으로 인지하는 단일클론항체 및 이의 용도
WO2015134877A1 (en) 2014-03-07 2015-09-11 Bellicum Pharmaceuticals, Inc. Caspase polypeptides having modified activity and uses thereof
ES2857226T3 (es) 2014-03-15 2021-09-28 Novartis Ag Receptor de antígeno quimérico regulable
FI3888674T3 (fi) 2014-04-07 2024-07-02 Novartis Ag Syövän hoito käyttäen kimeeristä anti-cd19-antigeenireseptoria
US20170029531A1 (en) 2014-04-09 2017-02-02 Seattle Children's Hospital (dba Seattle Children's Research Institute) Inhibition of lactate dehydrogenase 5 (ldh-5) binding, incorporation, internalization and/or endocytosis to immune cells
SG11201608393TA (en) 2014-04-10 2016-11-29 Seattle Children S Hospital Dba Seattle Children S Res Inst Transgene genetic tags and methods of use
KR20160145802A (ko) 2014-04-23 2016-12-20 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 요법에 사용하기 위한 키메라 항원 수용체 (car) 및 이의 제조 방법
WO2015167766A1 (en) 2014-04-29 2015-11-05 Seattle Children's Hospital (dba Seattle Children's Research Institute) Ccr5 disruption of cells expressing anti-hiv chimeric antigen receptor (car) derived from broadly neutralizing antibodies
WO2015188135A1 (en) 2014-06-06 2015-12-10 The California Institute For Biomedical Research Constant region antibody fusion proteins and compositions thereof
WO2015191874A1 (en) 2014-06-12 2015-12-17 Children's National Medical Center Generation of broadly-specific, virus-immune cells targeting multiple hiv antigens for preventive and therapeutic use
CN107109420A (zh) 2014-07-21 2017-08-29 诺华股份有限公司 使用cll－1嵌合抗原受体的癌症治疗
BR112017001242A2 (pt) 2014-07-21 2017-12-05 Novartis Ag tratamento de câncer usando um receptor antigênico quimérico a cd33
WO2016014565A2 (en) 2014-07-21 2016-01-28 Novartis Ag Treatment of cancer using humanized anti-bcma chimeric antigen receptor
EP3177640B1 (en) 2014-08-08 2020-05-06 The Board of Trustees of the Leland Stanford Junior University High affinity pd-1 agents and methods of use
WO2016025322A1 (en) 2014-08-09 2016-02-18 Purdue Research Foundation Design and development of neurokinin-1 receptor-binding agent delivery conjugates
CN106795497A (zh) 2014-08-12 2017-05-31 人类起源公司 被工程化以归巢至淋巴结b细胞区、皮肤或胃肠道的car‑t淋巴细胞
MY189028A (en) 2014-08-19 2022-01-20 Novartis Ag Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment
JP6868554B2 (ja) 2014-09-02 2021-05-12 ベリカム ファーマシューティカルズ， インコーポレイテッド ＭｙＤ８８およびＣＤ４０ポリペプチドによるキメラ抗原受容体の共刺激
WO2016044811A1 (en) 2014-09-19 2016-03-24 City Of Hope COSTIMULATORY CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING IL13Rα2
WO2016054520A2 (en) 2014-10-03 2016-04-07 The California Institute For Biomedical Research Engineered cell surface proteins and uses thereof
ES3015369T3 (en) 2014-10-09 2025-05-05 Seattle Childrens Hospital Dba Seattle Childrens Res Inst Long poly (a) plasmids and methods for introduction of long poly (a) sequences into the plasmid
KR102478073B1 (ko) 2014-10-14 2022-12-16 립타이드 바이오사이언스, 인코포레이티드 항-염증 특성을 갖는 펩타이드
JP7523203B2 (ja) 2014-10-31 2024-07-26 マサチューセッツ インスティテュート オブ テクノロジー 生体分子の免疫細胞への送達
HK1243441A1 (zh) 2014-11-05 2018-07-13 Board Of Regents, The University Of Texas System 基因修饰的免疫效应细胞和用於扩增免疫效应细胞的工程化细胞
US9879087B2 (en) 2014-11-12 2018-01-30 Siamab Therapeutics, Inc. Glycan-interacting compounds and methods of use
US10526573B2 (en) 2014-11-14 2020-01-07 Massachusetts Institute Of Technology Disruption and field enabled delivery of compounds and compositions into cells
EA037519B1 (ru) 2014-11-17 2021-04-07 Селлектар Байосайенсиз, Инк. Аналоги простых эфиров фосфолипидов в качестве носителей лекарственных средств, нацеленных на раковые клетки
BR112017011771A2 (pt) 2014-12-02 2018-07-10 Prospect Chartercare Rwmc Llc métodos e composições para o tratamento de câncer
KR102558502B1 (ko) 2014-12-05 2023-07-20 시티 오브 호프 Ｃｓ1 표적화된 키메라 항원 수용체-변형된 ｔ 세포
CA2966234A1 (en) 2014-12-15 2016-06-23 Bellicum Pharmaceuticals, Inc. Methods for controlled elimination of therapeutic cells
EP3608408A1 (en) 2014-12-15 2020-02-12 Bellicum Pharmaceuticals, Inc. Methods for controlled activation or elimination of therapeutic cells
US11253546B2 (en) 2014-12-15 2022-02-22 The Regents Of The University Of California Bispecific OR-gate chimeric antigen receptor responsive to CD19 and CD20
WO2016098078A2 (en) 2014-12-19 2016-06-23 Novartis Ag Dimerization switches and uses thereof
HRP20240357T1 (hr) 2014-12-24 2024-06-07 Autolus Limited Stanica
IL303247A (en) 2014-12-29 2023-07-01 Novartis Ag Methods for preparing cells expressing a chimeric receptor antigen
CN107249604A (zh) 2014-12-31 2017-10-13 人类起源公司 使用自然杀伤细胞治疗血液病症、实体瘤或感染性疾病的方法
US9765330B1 (en) 2015-01-09 2017-09-19 Nant Holdings Ip, Llc Compositions and methods for reduction of allograft recognition and rejection
KR102624023B1 (ko) 2015-02-24 2024-01-11 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 결합-촉발된 전사 스위치 및 이들의 이용 방법
CA2976684C (en) 2015-03-02 2024-03-05 Innovative Cellular Therapeutics CO., LTD. Reducing immune tolerance induced by pd-l1
EP3270936A4 (en) 2015-03-17 2018-08-08 Chimera Bioengineering Inc. Smart car devices, de car polypeptides, side cars and uses thereof
CA2984624A1 (en) 2015-03-18 2016-09-22 Baylor College Of Medicine Her2/erbb2 chimeric antigen receptor
US9717745B2 (en) 2015-03-19 2017-08-01 Zhejiang DTRM Biopharma Co. Ltd. Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases
WO2016154621A1 (en) 2015-03-26 2016-09-29 The California Institute For Biomedical Research SWITCHABLE NON-scFv CHIMERIC RECEPTORS, SWITCHES, AND USES THEREOF
US20180214527A1 (en) 2015-03-26 2018-08-02 City Of Hope Bi-specific targeted chimeric antigen receptor t cells
GB201505305D0 (en) 2015-03-27 2015-05-13 Immatics Biotechnologies Gmbh Novel Peptides and combination of peptides for use in immunotherapy against various tumors
WO2016168769A1 (en) 2015-04-15 2016-10-20 The California Institute For Biomedical Research Chimeric receptor t cell switches for her2
US11091546B2 (en) 2015-04-15 2021-08-17 The Scripps Research Institute Optimized PNE-based chimeric receptor T cell switches and uses thereof
CA2986030A1 (en) 2015-05-15 2016-11-24 City Of Hope Chimeric antigen receptor compositions
AU2016264363B2 (en) 2015-05-19 2019-07-25 Tuhura Biosciences, Inc. Cancer vaccine comprising mRNA encoding a M-like-protein
BR112017025166A2 (en) 2015-05-28 2018-07-31 Kite Pharma, Inc. Methods of Conditioning Patients for T-Cell Therapy
US9663756B1 (en) 2016-02-25 2017-05-30 Flodesign Sonics, Inc. Acoustic separation of cellular supporting materials from cultured cells
GB201514328D0 (en) 2015-08-12 2015-09-23 Sigmoid Pharma Ltd Compositions
GB201514874D0 (en) 2015-08-20 2015-10-07 Autolus Ltd Cell
GB201514875D0 (en) 2015-08-20 2015-10-07 Autolus Ltd Receptor
WO2017035362A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Use of complement pathway inhibitor compounds to mitigate adoptive t-cell therapy associated adverse immune responses
AU2016318773B2 (en) 2015-09-09 2024-08-01 Seattle Children's Hospital (dba Seattle Children's Research Institute) Genetic engineering of macrophages for immunotherapy
US9790467B2 (en) 2015-09-22 2017-10-17 Qt Holdings Corp Methods and compositions for activation or expansion of T lymphocytes
EP4108255A1 (en) 2015-10-05 2022-12-28 Precision Biosciences, Inc. Genetically-modified cells comprising a modified human t cell receptor alpha constant region gene
JP6985256B2 (ja) 2015-10-06 2021-12-22 シティ・オブ・ホープCity of Hope Ｐｓｃａを標的とするキメラ抗原レセプター
GB201518817D0 (en) 2015-10-23 2015-12-09 Autolus Ltd Cell
GB201518816D0 (en) 2015-10-23 2015-12-09 Autolus Ltd Receptor
CA3004299A1 (en) 2015-11-05 2017-05-11 City Of Hope Methods for preparing cells for adoptive t cell therapy
US20180327781A1 (en) 2015-11-09 2018-11-15 Seattle Children's Hospital (dba Seattle Children's Research Institute) Novel rna-based vector system for transient and stable gene expression
TWI724056B (zh) 2015-11-19 2021-04-11 美商卡默森屈有限公司 Ｃｘｃｒ２抑制劑
TWI734715B (zh) 2015-11-19 2021-08-01 美商卡默森屈有限公司 趨化因子受體調節劑
EP3390434A2 (en) 2015-12-14 2018-10-24 Bellicum Pharmaceuticals, Inc. Dual controls for therapeutic cell activation or elimination
US9849092B2 (en) 2015-12-21 2017-12-26 Gholam A. Peyman Early cancer detection and enhanced immunotherapy
EA201891589A1 (ru) 2016-01-08 2019-01-31 Те Риджентс Оф Те Юниверсити Оф Калифорния Условно активные гетеродимерные полипептиды и способы их применения
NZ743983A (en) 2016-01-11 2025-08-29 Univ Leland Stanford Junior Chimeric proteins and methods of regulating gene expression
EP3402509A4 (en) 2016-01-14 2019-07-10 Seattle Children's Hospital (DBA Seattle Children's Research Institute) TUMOR SPECIFIC IFNA SECRETION BY CAR T CELLS FOR RESTORING SOLID TUMOR MICRO ENVIRONMENT
AU2017213661B2 (en) 2016-02-05 2022-06-02 City Of Hope Administration of engineered T cells for treatment of cancers in the central nervous system
GB201602563D0 (en) 2016-02-12 2016-03-30 Autolus Ltd Signalling system
GB201602571D0 (en) 2016-02-12 2016-03-30 Autolus Ltd Signalling system
CN108697798A (zh) 2016-02-16 2018-10-23 达纳-法伯癌症研究所有限公司 免疫疗法组合物及方法
US11219635B2 (en) 2016-02-19 2022-01-11 City Of Hope Bi-specific aptamer
US11111505B2 (en) 2016-03-19 2021-09-07 Exuma Biotech, Corp. Methods and compositions for transducing lymphocytes and regulating the activity thereof
SG10202104509PA (en) 2016-03-19 2021-06-29 Exuma Biotech Corp Methods and compositions for transducing lymphocytes and regulated expansion thereof
JP7048571B2 (ja) 2016-03-22 2022-04-05 シアトル チルドレンズ ホスピタル （ディービーエイ シアトル チルドレンズ リサーチ インスティテュート） 毒性を予防または改善するための早期介入法
WO2017180587A2 (en) 2016-04-11 2017-10-19 Obsidian Therapeutics, Inc. Regulated biocircuit systems
CA3026640A1 (en) 2016-06-06 2017-12-14 City Of Hope Baff-r targeted chimeric antigen receptor-modified t-cells and uses thereof
EP4628094A2 (en) 2016-06-06 2025-10-08 City of Hope Baff-r antibodies and uses thereof
GB201610515D0 (en) 2016-06-16 2016-08-03 Autolus Ltd Cell
GB201610512D0 (en) 2016-06-16 2016-08-03 Autolus Ltd Chimeric antigen receptor
US9567399B1 (en) 2016-06-20 2017-02-14 Kymab Limited Antibodies and immunocytokines
CN115537372A (zh) 2016-07-13 2022-12-30 哈佛学院院长等 抗原呈递细胞模拟支架及其制备和使用方法
CN118853594A (zh) 2016-08-09 2024-10-29 希望之城 嵌合痘病毒组合物及其用途
US9642906B2 (en) 2016-09-16 2017-05-09 Baylor College Of Medicine Generation of HPV-specific T-cells
WO2018075813A1 (en) 2016-10-19 2018-04-26 City Of Hope Use of endogenous viral vaccine in chimeric antigen receptor t cell therapy
ES3030503T3 (en) 2016-10-19 2025-06-30 Scripps Research Inst Chimeric antigen receptor effector cell switches with humanized targeting moieties and/or optimized chimeric antigen receptor interacting domains and uses thereof
EP3529353A4 (en) 2016-10-19 2020-05-13 City of Hope USE OF TRIPLEX-CMV VACCINE IN CAR-T-CELL THERAPY
US10617720B2 (en) 2016-10-20 2020-04-14 Miltenyi Biotech, GmbH Chimeric antigen receptor specific for tumor cells
AU2016427822B2 (en) 2016-10-31 2025-01-23 Seattle Children's Hospital (dba Seattle Children's Research Institute) Method for treating autoimmune disease using CD4 T-cells with engineered stabilization of expression of endogennous FOXP3 gene
US20200095547A1 (en) 2016-12-02 2020-03-26 Darya ALIZADEH Methods for manufacturing t cells expressing of chimeric antigen receptors and other receptors
CN110291200B (zh) 2016-12-12 2024-05-14 西雅图儿童医院（Dba西雅图儿童研究所） 对哺乳动物细胞中转基因表达的药剂配体诱导具有增大的灵敏度的嵌合转录因子变异体
JP7206214B2 (ja) 2016-12-13 2023-01-17 シアトル チルドレンズ ホスピタル （ディービーエイ シアトル チルドレンズ リサーチ インスティテュート） インビトロ及びインビボで操作された細胞において発現された化学誘導シグナル伝達複合体の外因性薬物活性化の方法
EP3336107A1 (en) 2016-12-15 2018-06-20 Miltenyi Biotec GmbH Immune cells expressing an antigen binding receptor and a chimeric costimulatory receptor
CN110381989A (zh) 2016-12-21 2019-10-25 丹麦技术大学 用于免疫细胞操作的抗原呈递支架
EP3579870A4 (en) 2017-02-07 2020-12-30 Seattle Children's Hospital (DBA Seattle Children's Research Institute) PHOSPHOLIPID ETHER (PLE) T CAR-LYMPHOCYTE TUMOR (CTCT) TARGETING AGENTS
EP3583218B1 (en) 2017-02-17 2025-04-16 Purdue Research Foundation Targeted ligand-payload based drug delivery for cell therapy
WO2018160622A1 (en) 2017-02-28 2018-09-07 Endocyte, Inc. Compositions and methods for car t cell therapy
US20200276318A1 (en) 2017-03-06 2020-09-03 University Of Washington Engineered cells and agent compositions for therapeutic agent delivery and treatments using same
US20200405881A1 (en) 2017-03-06 2020-12-31 University Of Washington Cell based methods and compositions for therapeutic agent delivery and treatments using same
AU2018235957B2 (en) 2017-03-16 2024-02-01 Seattle Children's Hospital (dba Seattle Children's Research Institute) Engraftable cell-based immunotherapy for long-term delivery of therapeutic proteins
WO2018175453A1 (en) 2017-03-20 2018-09-27 City Of Hope Cs1 targeted chimeric antigen receptor-modified t cells for treatment of al amyloidosis
WO2018213332A1 (en) 2017-05-17 2018-11-22 Seattle Children's Hospital (dba Seattle Children's Research Institute) Generating mammalian t cell activation inducible synthetic promoters (syn+pro) to improve t cell therapy
EP3661558A4 (en) 2017-08-01 2021-08-11 City of Hope ANTI-IL1RAP ANTIBODIES
WO2019033050A1 (en) 2017-08-11 2019-02-14 City Of Hope BISPECIFIC MOLECULE FOR BINDING TO ANTIGEN
AU2019209432A1 (en) 2018-01-22 2020-08-06 Seattle Children's Hospital (dba Seattle Children's Research Institute) Methods of use for CAR T cells
CN111936518A (zh) 2018-02-06 2020-11-13 西雅图儿童医院（Dba西雅图儿童研究所） 对fl-ple标记的肿瘤表现出最佳的t细胞功能的荧光素特异性car
WO2019165237A1 (en) 2018-02-23 2019-08-29 Endocyte, Inc. Sequencing method for car t cell therapy
BR112020020887A2 (pt) 2018-04-12 2021-04-06 Umoja Biopharma, Inc Vetores virais e linhagens celulares de empacotamento
CA3091490A1 (en) 2018-04-27 2019-10-31 Seattle Children's Hospital (dba Seattle Children's Research Institute) Rapamycin resistant cells
CN112789051A (zh) 2018-08-06 2021-05-11 西雅图儿童医院（Dba西雅图儿童研究所） 用半抗原标记的细胞刺激嵌合抗原受体t细胞的方法和组合物
CA3108710A1 (en) 2018-08-07 2020-02-13 Purdue Research Foundation Rejuvenation of car t cell
WO2020106992A1 (en) 2018-11-21 2020-05-28 Umoja Biopharma, Inc. Multicistronic vector for surface engineering lentiviral particles
AU2020309505A1 (en) 2019-07-05 2022-01-27 Purdue Research Foundation Design and efficient synthesis of lipid-fluorescein conjugates for CAR-T cell therapy
CA3150890A1 (en) 2019-09-17 2021-03-25 Philip Stewart Low Fibroblast activation protein (fap)-targeted imaging and therapy of cancers and other fibrotic and inflammatory diseases
CN114981441A (zh) 2019-10-16 2022-08-30 优莫佳生物制药股份有限公司 用于通用受体疗法的逆转录病毒载体
IL295129A (en) 2020-01-30 2022-09-01 Umoja Biopharma Inc Bispecific transduction enhancer
CA3169804A1 (en) 2020-02-04 2021-08-12 Seattle Children's Hospital (dba Seattle Children's Research Institute) Methods and compositions for stimulation of chimeric antigen receptor t cells with hapten labelled cells
CA3169960A1 (en) 2020-02-04 2021-08-12 Seattle Children's Hospital (dba Seattle Children's Research Institute) Anti-dinitrophenol chimeric antigen receptors
BR112022017815A2 (pt) 2020-03-06 2022-11-29 Purdue Research Foundation Métodos, compostos e composições para modificar a atividade de células car-t
WO2022015955A1 (en) 2020-07-16 2022-01-20 Umoja Biopharma, Inc. Gated adapter targeting receptor
CA3199588A1 (en) 2020-11-20 2022-05-27 Andrew Scharenberg Vector system for delivery of multiple polynucleotides and uses thereof
CA3206009A1 (en) 2021-01-27 2022-08-04 Umoja Biopharma, Inc. Lentivirus for generating cells expressing anti-cd19 chimeric antigen receptor

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014100615A1 (en) 2012-12-20 2014-06-26 Purdue Research Foundation Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics
WO2016201300A1 (en) * 2015-06-12 2016-12-15 Immunomedics, Inc. Disease therapy with chimeric antigen receptor (car) constructs and t cells (car-t) or nk cells (car-nk) expressing car constructs
WO2017177149A2 (en) * 2016-04-08 2017-10-12 Purdue Research Foundation Methods and compositions for car t cell therapy

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ARTHRITIS RES THER, vol. 13, no. 2, 2011, pages R59
BAROCAS, DA ET AL.: "A Population-Based Study of Renal Cell Carcinoma and Prostate Cancer in the Same Patients", BJU INTERNATIONAL. JANUARY, vol. 97, no. 1, 6 December 2005 (2005-12-06), pages 33 - 36, XP055544776, Retrieved from the Internet <URL:https://doi.org/10.1111/j.1464-410X.2005.05880.x> *
DAVID T. RODGERS ET AL.: "Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies", PNAS, vol. 113, no. 4, 26 January 2016 (2016-01-26), pages 459 - E468, XP055260066, DOI: 10.1073/pnas.1524155113
JENNIFER S. Y. MA ET AL.: "Versatile strategy for controlling the specificity and activity of engineered T cells", PNAS, vol. 113, no. 4, 1 December 2016 (2016-12-01), pages 450 - 458
LAMERS, CH ET AL.: "Immune Responses to Transgene and Retroviral Vector in Patients Treated with Ex vivo-Engineered T Cells", BLOOD, vol. 117, no. 1, 1 October 2010 (2010-10-01), pages 72 - 82, XP055234814, Retrieved from the Internet <URL:doi:10.1182/blood-2010-07-294520> *
SAMBROOK ET AL.: "Molecular Cloning: A Laboratory Manual", 2012, COLD SPRING HARBOR LABORATORY PRESS

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12150981B2 (en) 2012-12-20 2024-11-26 Purdue Research Foundation Chimeric antigen receptor-expressing T cells as anti-cancer therapeutics
US11225520B2 (en) 2016-02-16 2022-01-18 Dana-Farber Cancer Institute, Inc. Immunotherapy compositions and methods
US12144850B2 (en) 2016-04-08 2024-11-19 Purdue Research Foundation Methods and compositions for car T cell therapy
EP3439675A4 (en) * 2016-04-08 2019-12-18 Purdue Research Foundation METHOD AND COMPOSITIONS FOR CAR-T CELL THERAPY
US11649288B2 (en) 2017-02-07 2023-05-16 Seattle Children's Hospital Phospholipid ether (PLE) CAR T cell tumor targeting (CTCT) agents
US11850262B2 (en) 2017-02-28 2023-12-26 Purdue Research Foundation Compositions and methods for CAR T cell therapy
US11759480B2 (en) 2017-02-28 2023-09-19 Endocyte, Inc. Compositions and methods for CAR T cell therapy
US11524082B2 (en) 2017-08-22 2022-12-13 Purdue Research Foundation FBSA-based therapeutic and radioimaging conjugates targeting carbonic anhydrase positive cancers
EP3672615A4 (en) * 2017-08-22 2021-04-21 Purdue Research Foundation FBSA-BASED THERAPEUTIC AND RADIO IMAGING CONJUGATES AGAINST CARBOAN HYDRASE-POSITIVE CANCER TYPES
US12269862B2 (en) 2018-01-22 2025-04-08 Endocyte, Inc. Methods of use for CAR T cells
US11311576B2 (en) 2018-01-22 2022-04-26 Seattle Children's Hospital Methods of use for CAR T cells
WO2019144095A1 (en) * 2018-01-22 2019-07-25 Seattle Children's Hospital (dba Seattle Children's Research Institute) Methods of use for car t cells
US11779602B2 (en) 2018-01-22 2023-10-10 Endocyte, Inc. Methods of use for CAR T cells
WO2019144091A1 (en) * 2018-01-22 2019-07-25 Endocyte, Inc. Methods of use for car t cells
US12312416B2 (en) 2018-02-06 2025-05-27 Seattle Children's Hospital Fluorescein-specific cars exhibiting optimal t cell function against FL-PLE labelled tumors
EP3755366A4 (en) * 2018-02-23 2021-12-29 Endocyte, Inc. Sequencing method for car t cell therapy
US12240870B2 (en) 2018-02-23 2025-03-04 Purdue Research Foundation Sequencing method for CAR T cell therapy
US12466869B2 (en) 2018-06-28 2025-11-11 Dana-Farber Cancer Institute, Inc. Targeting of multiple antigens with multiplex CAR T cells in solid and liquid malignancies
JP2022525400A (ja) * 2019-03-13 2022-05-13 シアトル チルドレンズ ホスピタル （ディービーエイ シアトル チルドレンズ リサーチ インスティテュート） フルオレセインエーテルリン脂質またはフルオレセインエーテルリン脂質前駆体と併用した抗フルオレセインｃａｒ ｔ細胞に対する拮抗薬としてのフルオレセインナトリウム
WO2020185917A1 (en) * 2019-03-13 2020-09-17 Seattle Children's Hospital (dba Seattle Children's Research Institute) Sodium fluorescein as a reversal agent for an anti-fluorescein car t cells and fluorescein-phospholipid-ethers or profluorescein-phospholipid-ethers
WO2024121297A1 (en) 2022-12-09 2024-06-13 Avencell Europe Gmbh A kit for use in the treatment of hematological cancer
EP4382119A1 (en) 2022-12-09 2024-06-12 AvenCell Europe GmbH A kit for use in the treatment of hematological cancer

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US11850262B2 (en) 2023-12-26
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