CA2656583A1 - Anticorps utiles en tant qu'analogues de recepteur des lymphocytes t, leurs procedes de production et leurs utilisations - Google Patents
Anticorps utiles en tant qu'analogues de recepteur des lymphocytes t, leurs procedes de production et leurs utilisations Download PDFInfo
- Publication number
- CA2656583A1 CA2656583A1 CA002656583A CA2656583A CA2656583A1 CA 2656583 A1 CA2656583 A1 CA 2656583A1 CA 002656583 A CA002656583 A CA 002656583A CA 2656583 A CA2656583 A CA 2656583A CA 2656583 A1 CA2656583 A1 CA 2656583A1
- Authority
- CA
- Canada
- Prior art keywords
- peptide
- cells
- hla
- mhc
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 145
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title claims description 113
- 108091008874 T cell receptors Proteins 0.000 title claims description 111
- 238000004519 manufacturing process Methods 0.000 title description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 693
- 210000004027 cell Anatomy 0.000 claims description 590
- 230000027455 binding Effects 0.000 claims description 130
- 241000282414 Homo sapiens Species 0.000 claims description 116
- 230000003278 mimic effect Effects 0.000 claims description 82
- 230000002163 immunogen Effects 0.000 claims description 76
- 241000699670 Mus sp. Species 0.000 claims description 73
- 210000004408 hybridoma Anatomy 0.000 claims description 66
- 230000009089 cytolysis Effects 0.000 claims description 50
- 150000001413 amino acids Chemical class 0.000 claims description 48
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 47
- 210000002966 serum Anatomy 0.000 claims description 42
- 230000003053 immunization Effects 0.000 claims description 26
- 230000001225 therapeutic effect Effects 0.000 claims description 26
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 25
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 25
- 108010090804 Streptavidin Proteins 0.000 claims description 24
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 24
- 239000000758 substrate Substances 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 17
- 150000007523 nucleic acids Chemical class 0.000 claims description 14
- 230000028993 immune response Effects 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 12
- 108090000790 Enzymes Proteins 0.000 claims description 12
- 102000039446 nucleic acids Human genes 0.000 claims description 12
- 108020004707 nucleic acids Proteins 0.000 claims description 12
- 102000004127 Cytokines Human genes 0.000 claims description 10
- 108090000695 Cytokines Proteins 0.000 claims description 10
- 230000001472 cytotoxic effect Effects 0.000 claims description 9
- 230000004048 modification Effects 0.000 claims description 9
- 238000012986 modification Methods 0.000 claims description 9
- 238000011830 transgenic mouse model Methods 0.000 claims description 9
- 241000282412 Homo Species 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000011324 bead Substances 0.000 claims description 6
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 6
- 230000006641 stabilisation Effects 0.000 claims description 6
- 238000011105 stabilization Methods 0.000 claims description 6
- 230000009261 transgenic effect Effects 0.000 claims description 6
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 5
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 5
- 238000007413 biotinylation Methods 0.000 claims description 5
- 230000006287 biotinylation Effects 0.000 claims description 5
- 231100000433 cytotoxic Toxicity 0.000 claims description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 4
- 239000002502 liposome Substances 0.000 claims description 4
- 210000004180 plasmocyte Anatomy 0.000 claims description 4
- 102000019260 B-Cell Antigen Receptors Human genes 0.000 claims description 3
- 108010012919 B-Cell Antigen Receptors Proteins 0.000 claims description 3
- 241000700159 Rattus Species 0.000 claims description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 3
- 238000010382 chemical cross-linking Methods 0.000 claims description 3
- 238000005538 encapsulation Methods 0.000 claims description 3
- 231100000331 toxic Toxicity 0.000 claims description 3
- 230000002588 toxic effect Effects 0.000 claims description 3
- 241000699800 Cricetinae Species 0.000 claims description 2
- 108010006519 Molecular Chaperones Proteins 0.000 claims description 2
- 102000005431 Molecular Chaperones Human genes 0.000 claims description 2
- 241000282520 Papio Species 0.000 claims description 2
- 238000010212 intracellular staining Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 description 161
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 127
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 127
- 210000004881 tumor cell Anatomy 0.000 description 117
- 102000004196 processed proteins & peptides Human genes 0.000 description 107
- 101150029707 ERBB2 gene Proteins 0.000 description 92
- 238000010186 staining Methods 0.000 description 91
- 102000012858 Eukaryotic Initiation Factor-4G Human genes 0.000 description 88
- 108010057192 Eukaryotic Initiation Factor-4G Proteins 0.000 description 88
- 239000000427 antigen Substances 0.000 description 84
- 108091007433 antigens Proteins 0.000 description 84
- 102000036639 antigens Human genes 0.000 description 84
- 108090000623 proteins and genes Proteins 0.000 description 80
- 230000014509 gene expression Effects 0.000 description 70
- 239000000178 monomer Substances 0.000 description 65
- 102000004169 proteins and genes Human genes 0.000 description 65
- 235000018102 proteins Nutrition 0.000 description 62
- 238000003556 assay Methods 0.000 description 60
- 201000011510 cancer Diseases 0.000 description 58
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 58
- 235000001014 amino acid Nutrition 0.000 description 54
- 238000002965 ELISA Methods 0.000 description 53
- 229940024606 amino acid Drugs 0.000 description 48
- 206010006187 Breast cancer Diseases 0.000 description 45
- 208000026310 Breast neoplasm Diseases 0.000 description 45
- 210000001744 T-lymphocyte Anatomy 0.000 description 42
- 239000006228 supernatant Substances 0.000 description 40
- 239000011534 wash buffer Substances 0.000 description 39
- 238000004458 analytical method Methods 0.000 description 35
- 238000007792 addition Methods 0.000 description 32
- 241000283707 Capra Species 0.000 description 31
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Natural products N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 30
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 30
- 239000000523 sample Substances 0.000 description 29
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 28
- 238000010790 dilution Methods 0.000 description 27
- 239000012895 dilution Substances 0.000 description 27
- 125000003275 alpha amino acid group Chemical group 0.000 description 26
- 108091033319 polynucleotide Proteins 0.000 description 26
- 102000040430 polynucleotide Human genes 0.000 description 26
- 239000002157 polynucleotide Substances 0.000 description 26
- 108060003951 Immunoglobulin Proteins 0.000 description 25
- 102000018358 immunoglobulin Human genes 0.000 description 25
- 229920001184 polypeptide Polymers 0.000 description 25
- 230000009257 reactivity Effects 0.000 description 24
- 230000009870 specific binding Effects 0.000 description 24
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 23
- 239000012634 fragment Substances 0.000 description 23
- 239000002953 phosphate buffered saline Substances 0.000 description 23
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 22
- 238000001514 detection method Methods 0.000 description 22
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 21
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 21
- 239000000872 buffer Substances 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000003446 ligand Substances 0.000 description 20
- 238000011282 treatment Methods 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 238000002649 immunization Methods 0.000 description 19
- 235000013336 milk Nutrition 0.000 description 19
- 239000008267 milk Substances 0.000 description 19
- 210000004080 milk Anatomy 0.000 description 19
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 18
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 229960002685 biotin Drugs 0.000 description 16
- 235000020958 biotin Nutrition 0.000 description 16
- 239000011616 biotin Substances 0.000 description 16
- 238000011161 development Methods 0.000 description 16
- 238000000684 flow cytometry Methods 0.000 description 16
- 208000015181 infectious disease Diseases 0.000 description 16
- 239000002773 nucleotide Substances 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 238000013459 approach Methods 0.000 description 15
- 238000012512 characterization method Methods 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 238000012216 screening Methods 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 13
- 108091034117 Oligonucleotide Proteins 0.000 description 13
- 102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 13
- 230000000295 complement effect Effects 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 238000003118 sandwich ELISA Methods 0.000 description 13
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 12
- 239000012228 culture supernatant Substances 0.000 description 12
- 230000001419 dependent effect Effects 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 238000011534 incubation Methods 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 239000013638 trimer Substances 0.000 description 12
- 231100000588 tumorigenic Toxicity 0.000 description 12
- 230000000381 tumorigenic effect Effects 0.000 description 12
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 11
- 230000002458 infectious effect Effects 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 241000894007 species Species 0.000 description 11
- 230000004614 tumor growth Effects 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 10
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 10
- 108091054437 MHC class I family Proteins 0.000 description 10
- 201000008275 breast carcinoma Diseases 0.000 description 10
- 230000002950 deficient Effects 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 10
- 229940072221 immunoglobulins Drugs 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 238000007423 screening assay Methods 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 9
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 9
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 9
- 241001529936 Murinae Species 0.000 description 9
- 102100040247 Tumor necrosis factor Human genes 0.000 description 9
- 230000005875 antibody response Effects 0.000 description 9
- 230000006037 cell lysis Effects 0.000 description 9
- 239000000539 dimer Substances 0.000 description 9
- 230000003211 malignant effect Effects 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 8
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 238000003125 immunofluorescent labeling Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 201000001441 melanoma Diseases 0.000 description 8
- 239000013642 negative control Substances 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 238000010200 validation analysis Methods 0.000 description 8
- -1 264 Proteins 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
- 102100034013 Gamma-glutamyl phosphate reductase Human genes 0.000 description 7
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 7
- 241000725303 Human immunodeficiency virus Species 0.000 description 7
- 241000699660 Mus musculus Species 0.000 description 7
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000012875 competitive assay Methods 0.000 description 7
- 230000002860 competitive effect Effects 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 230000002147 killing effect Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 6
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000012286 ELISA Assay Methods 0.000 description 6
- 101100527991 Human cytomegalovirus (strain Merlin) RL9A gene Proteins 0.000 description 6
- 102000043129 MHC class I family Human genes 0.000 description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 description 6
- 102100037434 Probable ATP-dependent RNA helicase DDX5 Human genes 0.000 description 6
- 230000030741 antigen processing and presentation Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 210000004443 dendritic cell Anatomy 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- AHOKKYCUWBLDST-QYULHYBRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2,6-diaminohexanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)[C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=CC=C1 AHOKKYCUWBLDST-QYULHYBRSA-N 0.000 description 5
- 102210024302 HLA-B*0702 Human genes 0.000 description 5
- 108010078301 HLA-B*07:02 antigen Proteins 0.000 description 5
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- 206010033128 Ovarian cancer Diseases 0.000 description 5
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 210000002919 epithelial cell Anatomy 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 229960000310 isoleucine Drugs 0.000 description 5
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 238000001542 size-exclusion chromatography Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 206010057248 Cell death Diseases 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 4
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 4
- 102000011786 HLA-A Antigens Human genes 0.000 description 4
- 108010075704 HLA-A Antigens Proteins 0.000 description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 4
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 4
- 101000655352 Homo sapiens Telomerase reverse transcriptase Proteins 0.000 description 4
- 101100472044 Human cytomegalovirus (strain Merlin) RL8A gene Proteins 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- 231100000416 LDH assay Toxicity 0.000 description 4
- 102000003960 Ligases Human genes 0.000 description 4
- 108090000364 Ligases Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 102000003992 Peroxidases Human genes 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 239000012505 Superdex™ Substances 0.000 description 4
- 230000024932 T cell mediated immunity Effects 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 4
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 238000011717 athymic nude mouse Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 108091005948 blue fluorescent proteins Proteins 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 230000009137 competitive binding Effects 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 239000005090 green fluorescent protein Substances 0.000 description 4
- 210000003000 inclusion body Anatomy 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 108010086642 reticulocalbin Proteins 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 208000011691 Burkitt lymphomas Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 101100090376 Human cytomegalovirus (strain Merlin) RL5A gene Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- 108010033276 Peptide Fragments Proteins 0.000 description 3
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 3
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 3
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 3
- 108010017842 Telomerase Proteins 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 229940034982 antineoplastic agent Drugs 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 201000010536 head and neck cancer Diseases 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 229940022353 herceptin Drugs 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 229940127121 immunoconjugate Drugs 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 108010082117 matrigel Proteins 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000000611 regression analysis Methods 0.000 description 3
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000008093 supporting effect Effects 0.000 description 3
- 210000001550 testis Anatomy 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 2
- 102100030346 Antigen peptide transporter 1 Human genes 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108010023729 Complement 3d Receptors Proteins 0.000 description 2
- 102100032768 Complement receptor type 2 Human genes 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 238000000729 Fisher's exact test Methods 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 108010035452 HLA-A1 Antigen Proteins 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 206010064912 Malignant transformation Diseases 0.000 description 2
- 108010023335 Member 2 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- 241001644525 Nastus productus Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 101800001357 Potential peptide Proteins 0.000 description 2
- 102400000745 Potential peptide Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 206010054094 Tumour necrosis Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 2
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 2
- 238000013357 binding ELISA Methods 0.000 description 2
- 125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 2
- 101150031021 birA gene Proteins 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000002619 cancer immunotherapy Methods 0.000 description 2
- 239000012830 cancer therapeutic Substances 0.000 description 2
- 238000009566 cancer vaccine Methods 0.000 description 2
- 229940022399 cancer vaccine Drugs 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 231100000315 carcinogenic Toxicity 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000002784 cytotoxicity assay Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000001917 fluorescence detection Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 210000004754 hybrid cell Anatomy 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 239000012642 immune effector Substances 0.000 description 2
- 210000004201 immune sera Anatomy 0.000 description 2
- 229940042743 immune sera Drugs 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 230000036212 malign transformation Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 108091005601 modified peptides Proteins 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- ZDZOTLJHXYCWBA-BSEPLHNVSA-N molport-006-823-826 Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-BSEPLHNVSA-N 0.000 description 2
- 230000000869 mutational effect Effects 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 229960002087 pertuzumab Drugs 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 108010044720 telomerase reverse transcriptase (540-548) Proteins 0.000 description 2
- 230000002381 testicular Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
- SSOORFWOBGFTHL-OTEJMHTDSA-N (4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SSOORFWOBGFTHL-OTEJMHTDSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- PRCNDINHAAMLFD-UHFFFAOYSA-N 2-[[2-[[2-[[2-[[2-[[6-amino-2-[2-[[2-[(2-amino-3-methylpentanoyl)amino]-4-methylpentanoyl]amino]propanoylamino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-4-methy Chemical compound C=1N=CNC=1CC(C(=O)NC(CC=1C2=CC=CC=C2NC=1)C(=O)NC(CC(C)C)C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(C)NC(=O)C(CC(C)C)NC(=O)C(N)C(C)CC)CC1=CC=CC=C1 PRCNDINHAAMLFD-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 238000000035 BCA protein assay Methods 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 102100028243 Breast carcinoma-amplified sequence 1 Human genes 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 108090000538 Caspase-8 Proteins 0.000 description 1
- 101710150820 Cellular tumor antigen p53 Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000011412 Complement 3d Receptors Human genes 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 102000007120 DEAD-box RNA Helicases Human genes 0.000 description 1
- 108010033333 DEAD-box RNA Helicases Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 101100072149 Drosophila melanogaster eIF2alpha gene Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 238000011510 Elispot assay Methods 0.000 description 1
- 208000032163 Emerging Communicable disease Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 108010013476 HLA-A24 Antigen Proteins 0.000 description 1
- 108010034115 HLA-A29 antigen Proteins 0.000 description 1
- 108010091938 HLA-B7 Antigen Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000935635 Homo sapiens Breast carcinoma-amplified sequence 1 Proteins 0.000 description 1
- 101000883515 Homo sapiens Chitinase-3-like protein 1 Proteins 0.000 description 1
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101001133081 Homo sapiens Mucin-2 Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JZKXXXDKRQWDET-QMMMGPOBSA-N L-m-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-QMMMGPOBSA-N 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 206010060880 Monoclonal gammopathy Diseases 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 102100034263 Mucin-2 Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 101000822667 Mus musculus Something about silencing protein 10 Proteins 0.000 description 1
- DTERQYGMUDWYAZ-ZETCQYMHSA-N N(6)-acetyl-L-lysine Chemical compound CC(=O)NCCCC[C@H]([NH3+])C([O-])=O DTERQYGMUDWYAZ-ZETCQYMHSA-N 0.000 description 1
- JJIHLJJYMXLCOY-BYPYZUCNSA-N N-acetyl-L-serine Chemical compound CC(=O)N[C@@H](CO)C(O)=O JJIHLJJYMXLCOY-BYPYZUCNSA-N 0.000 description 1
- PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 208000022639 SchC6pf-Schulz-Passarge syndrome Diseases 0.000 description 1
- 208000001364 Schopf-Schulz-Passarge syndrome Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102100032938 Telomerase reverse transcriptase Human genes 0.000 description 1
- 241001197925 Theila Species 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 241000710886 West Nile virus Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 102000006707 alpha-beta T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010087408 alpha-beta T-Cell Antigen Receptors Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000003127 anti-melanomic effect Effects 0.000 description 1
- 230000002788 anti-peptide Effects 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000003443 bladder cell Anatomy 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000007295 breast benign neoplasm Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 230000003034 chemosensitisation Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940015047 chorionic gonadotropin Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012468 concentrated sample Substances 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000009402 cross-breeding Methods 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- PGUYAANYCROBRT-UHFFFAOYSA-N dihydroxy-selanyl-selanylidene-lambda5-phosphane Chemical compound OP(O)([SeH])=[Se] PGUYAANYCROBRT-UHFFFAOYSA-N 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 1
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 1
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 1
- 229960002733 gamolenic acid Drugs 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 125000003712 glycosamine group Chemical group 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 108010021083 hen egg lysozyme Proteins 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 102000054350 human CHI3L1 Human genes 0.000 description 1
- 102000055647 human CSF2RB Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 229940032219 immunotherapy vaccine Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 108010028930 invariant chain Proteins 0.000 description 1
- 208000030776 invasive breast carcinoma Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 201000010893 malignant breast melanoma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000012577 media supplement Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000004160 naive b lymphocyte Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 108700025694 p53 Genes Proteins 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 238000005222 photoaffinity labeling Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 230000030788 protein refolding Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009712 regulation of translation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000028710 ribosome assembly Effects 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 201000003804 salivary gland carcinoma Diseases 0.000 description 1
- JRPHGDYSKGJTKZ-UHFFFAOYSA-K selenophosphate Chemical compound [O-]P([O-])([O-])=[Se] JRPHGDYSKGJTKZ-UHFFFAOYSA-K 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 231100000188 sister chromatid exchange Toxicity 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 108091006108 transcriptional coactivators Proteins 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 239000000225 tumor suppressor protein Substances 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/3015—Breast
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/3053—Skin, nerves, brain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US81007906P | 2006-06-01 | 2006-06-01 | |
US60/810,079 | 2006-06-01 | ||
US11/517,516 US20070092530A1 (en) | 2004-05-27 | 2006-09-07 | Antibodies as T cell receptor mimics, methods of production and uses thereof |
US11/517,516 | 2006-09-07 | ||
PCT/US2007/012958 WO2007143104A2 (fr) | 2006-06-01 | 2007-06-01 | Anticorps utiles en tant qu'analogues de récepteur des lymphocytes t, leurs procédés de production et leurs utilisations |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2656583A1 true CA2656583A1 (fr) | 2007-12-13 |
Family
ID=40262722
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002656583A Abandoned CA2656583A1 (fr) | 2006-06-01 | 2007-06-01 | Anticorps utiles en tant qu'analogues de recepteur des lymphocytes t, leurs procedes de production et leurs utilisations |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP2026837A4 (fr) |
AU (1) | AU2007254859A1 (fr) |
CA (1) | CA2656583A1 (fr) |
IL (1) | IL195470A0 (fr) |
WO (1) | WO2007143104A2 (fr) |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009108372A2 (fr) * | 2008-02-27 | 2009-09-03 | Receptor Logic, Inc. | Anticorps imitant les récepteurs des lymphocytes t, leurs procédés de production et d’utilisation |
NL2014935B1 (en) * | 2015-06-08 | 2017-02-03 | Applied Immune Tech Ltd | T cell receptor like antibodies having fine specificity. |
CN115927191A (zh) | 2015-10-23 | 2023-04-07 | 优瑞科生物技术公司 | 抗体/t细胞受体嵌合构建体及其用途 |
GB201520565D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520536D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520575D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520558D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520548D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520562D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520559D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520557D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520539D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520550D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520542D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520545D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520566D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520579D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520583D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520589D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520546D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201607534D0 (en) | 2016-04-29 | 2016-06-15 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201607535D0 (en) | 2016-04-29 | 2016-06-15 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520603D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520567D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
WO2017089786A1 (fr) | 2015-11-23 | 2017-06-01 | Immunocore Limited | Peptides |
GB201520595D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520568D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd | Peptides |
GB201520564D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520544D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520563D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520543D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201604468D0 (en) | 2016-03-16 | 2016-04-27 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520592D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520541D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
GB201520570D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
WO2018083505A1 (fr) | 2016-11-07 | 2018-05-11 | Immunocore Limited | Peptides |
GB201520597D0 (en) | 2015-11-23 | 2016-01-06 | Immunocore Ltd & Adaptimmune Ltd | Peptides |
JP2019517499A (ja) | 2016-06-02 | 2019-06-24 | イムノコア リミテッド | gp100特異的TCR−抗CD3 scFv融合タンパク質の投薬レジメン |
AU2018258046A1 (en) | 2017-04-26 | 2019-12-12 | Eureka Therapeutics, Inc. | Cells expressing chimeric activating receptors and chimeric stimulating receptors and uses thereof |
US11485785B2 (en) | 2017-06-14 | 2022-11-01 | Adicet Bio, Inc. | Antibodies capable of binding HLA-A2/TyrD in an HLA restricted manner and uses thereof |
GB201815041D0 (en) | 2018-09-14 | 2018-10-31 | Scancell Ltd | Epitopes |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL155307A0 (en) * | 2000-10-10 | 2003-11-23 | Univ Oklahoma | Methods for isolating, identifying and purifying peptide ligands and peptide ligands produced thereby |
US20050003483A1 (en) * | 2000-10-10 | 2005-01-06 | Hildebrand William H. | Comparative ligand mapping from MHC class 1 positive cells |
EP1485075A4 (fr) * | 2002-02-20 | 2006-04-26 | Dyax Corp | Ligands de liaison au complexe mhc-peptide |
US20070105779A1 (en) * | 2002-07-31 | 2007-05-10 | Danila Valmori | Isolated, ssx-2 and ssx-2 related peptides useful as hla binders and ctl epitopes, and uses thereof |
US20060034850A1 (en) * | 2004-05-27 | 2006-02-16 | Weidanz Jon A | Antibodies as T cell receptor mimics, methods of production and uses thereof |
CA2662798A1 (fr) * | 2005-09-07 | 2007-03-15 | Receptor Logic, Ltd. | Anticorps utilises comme mimetiques de recepteurs de lymphocytes t, leurs methodes de production et leurs applications |
-
2007
- 2007-06-01 AU AU2007254859A patent/AU2007254859A1/en not_active Abandoned
- 2007-06-01 EP EP07777355A patent/EP2026837A4/fr not_active Withdrawn
- 2007-06-01 CA CA002656583A patent/CA2656583A1/fr not_active Abandoned
- 2007-06-01 WO PCT/US2007/012958 patent/WO2007143104A2/fr active Application Filing
-
2008
- 2008-11-24 IL IL195470A patent/IL195470A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
EP2026837A4 (fr) | 2010-06-02 |
IL195470A0 (en) | 2011-08-01 |
AU2007254859A1 (en) | 2007-12-13 |
WO2007143104A8 (fr) | 2008-07-31 |
WO2007143104A2 (fr) | 2007-12-13 |
EP2026837A2 (fr) | 2009-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20090226474A1 (en) | Antibodies as T cell receptor mimics, methods of production and uses thereof | |
CA2567814C (fr) | Anticorps mimetiques de recepteurs de cellules t et leurs procedes de production et d'utilisation | |
CA2656583A1 (fr) | Anticorps utiles en tant qu'analogues de recepteur des lymphocytes t, leurs procedes de production et leurs utilisations | |
US20110293623A1 (en) | Antibodies as t cell receptor mimics, methods of production and uses thereof | |
US20140065708A1 (en) | Antibodies as t cell receptor mimics, methods of production and uses thereof | |
AU2016276555B2 (en) | T cell receptor like antibodies having fine specificity | |
JP2019521643A (ja) | Cd80バリアント免疫調節タンパク質およびその使用 | |
US20100158927A1 (en) | Antibodies, methods and kits for diagnosing and treating melanoma | |
KR20180016972A (ko) | Cd137에 결합하는 항체 치료제 | |
US11999793B2 (en) | Therapeutic anti-CD9 antibody | |
US20180179283A1 (en) | T cell receptor like antibodies having fine specificity | |
KR20200131260A (ko) | 가용성 면역 수용체 cd28을 감소시키기 위한 방법 및 조성물 | |
EP2262834A2 (fr) | Anticorps imitant les récepteurs des lymphocytes t, leurs procédés de production et d utilisation | |
AU2006289683A1 (en) | Antibodies as T cell receptor mimics, methods of production and uses thereof | |
WO2023178357A1 (fr) | Molécules de fusion d'anticorps bispécifiques et leurs procédés d'utilisation | |
US20160017031A1 (en) | T cell receptor mimic rl9a | |
US20230046744A1 (en) | Methods and means for attracting immune effector cells to tumor cells | |
EP1182210A1 (fr) | Epitopes de l'antigène MUC1 associé aux tumeurs | |
US20210388109A1 (en) | Compositions and methods regarding engineered and non-engineered gamma delta t-cells for treatment of solid tumors | |
US20220017636A1 (en) | Mageb2 binding constructs | |
CA3205170A1 (fr) | Lymphocytes t destines a etre utilises en therapie | |
Miller | Use of T cell receptor-like antibody fragments for imaging and immunotherapy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
FZDE | Discontinued |
Effective date: 20140603 |