JP2021520209A - 癌患者における腫瘍抗原を検出するための診断アッセイ - Google Patents
癌患者における腫瘍抗原を検出するための診断アッセイ Download PDFInfo
- Publication number
- JP2021520209A JP2021520209A JP2020554287A JP2020554287A JP2021520209A JP 2021520209 A JP2021520209 A JP 2021520209A JP 2020554287 A JP2020554287 A JP 2020554287A JP 2020554287 A JP2020554287 A JP 2020554287A JP 2021520209 A JP2021520209 A JP 2021520209A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- car
- cell
- antigen
- domain
- 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.)
- Pending
Links
- 239000000427 antigen Substances 0.000 title claims abstract description 267
- 108091007433 antigens Proteins 0.000 title claims abstract description 265
- 102000036639 antigens Human genes 0.000 title claims abstract description 265
- 238000003556 assay Methods 0.000 title claims abstract description 112
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 60
- 201000011510 cancer Diseases 0.000 title claims abstract description 21
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 169
- 230000014509 gene expression Effects 0.000 claims abstract description 76
- 239000013610 patient sample Substances 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 350
- 230000027455 binding Effects 0.000 claims description 246
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 163
- 230000011664 signaling Effects 0.000 claims description 122
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 83
- 108700008625 Reporter Genes Proteins 0.000 claims description 66
- 210000004881 tumor cell Anatomy 0.000 claims description 48
- 230000004913 activation Effects 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 44
- 108091027981 Response element Proteins 0.000 claims description 41
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims description 36
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims description 36
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 30
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 30
- 230000003834 intracellular effect Effects 0.000 claims description 29
- 239000000523 sample Substances 0.000 claims description 25
- 230000037361 pathway Effects 0.000 claims description 18
- 108010043121 Green Fluorescent Proteins Proteins 0.000 claims description 17
- 108060001084 Luciferase Proteins 0.000 claims description 16
- 239000005089 Luciferase Substances 0.000 claims description 16
- 102000004144 Green Fluorescent Proteins Human genes 0.000 claims description 15
- 239000005090 green fluorescent protein Substances 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 14
- 108010057466 NF-kappa B Proteins 0.000 claims description 13
- 230000006044 T cell activation Effects 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 230000004068 intracellular signaling Effects 0.000 claims description 10
- 108010018242 Transcription Factor AP-1 Proteins 0.000 claims description 9
- 230000000259 anti-tumor effect Effects 0.000 claims description 8
- 108010001857 Cell Surface Receptors Proteins 0.000 claims description 5
- 102000006830 Luminescent Proteins Human genes 0.000 claims description 4
- 108010047357 Luminescent Proteins Proteins 0.000 claims description 4
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 claims description 4
- 101710160107 Outer membrane protein A Proteins 0.000 claims description 4
- 102000000844 Cell Surface Receptors Human genes 0.000 claims 1
- 102100023118 Transcription factor JunD Human genes 0.000 claims 1
- 238000002619 cancer immunotherapy Methods 0.000 abstract description 8
- 238000010586 diagram Methods 0.000 abstract description 8
- 230000004044 response Effects 0.000 abstract description 8
- 238000004113 cell culture Methods 0.000 abstract description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 110
- 102000004196 processed proteins & peptides Human genes 0.000 description 91
- 108090000623 proteins and genes Proteins 0.000 description 89
- 229920001184 polypeptide Polymers 0.000 description 78
- 239000012634 fragment Substances 0.000 description 65
- 102000004169 proteins and genes Human genes 0.000 description 65
- 235000018102 proteins Nutrition 0.000 description 61
- 235000001014 amino acid Nutrition 0.000 description 50
- 150000001413 amino acids Chemical class 0.000 description 44
- 150000007523 nucleic acids Chemical class 0.000 description 38
- 102000005962 receptors Human genes 0.000 description 37
- 108020003175 receptors Proteins 0.000 description 37
- 102000039446 nucleic acids Human genes 0.000 description 34
- 108020004707 nucleic acids Proteins 0.000 description 34
- 241000699666 Mus <mouse, genus> Species 0.000 description 28
- 239000013598 vector Substances 0.000 description 28
- 108091028043 Nucleic acid sequence Proteins 0.000 description 27
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 26
- 102100022748 Wilms tumor protein Human genes 0.000 description 26
- 101710127857 Wilms tumor protein Proteins 0.000 description 26
- 238000004020 luminiscence type Methods 0.000 description 25
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 24
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 24
- 102000040430 polynucleotide Human genes 0.000 description 23
- 108091033319 polynucleotide Proteins 0.000 description 23
- 239000002157 polynucleotide Substances 0.000 description 23
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 22
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 239000013604 expression vector Substances 0.000 description 20
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 19
- -1 FolR1 Proteins 0.000 description 19
- 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 19
- 239000002953 phosphate buffered saline Substances 0.000 description 19
- 108060003951 Immunoglobulin Proteins 0.000 description 17
- 102000018358 immunoglobulin Human genes 0.000 description 17
- 238000001514 detection method Methods 0.000 description 16
- 108020004414 DNA Proteins 0.000 description 15
- 238000011534 incubation Methods 0.000 description 15
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 14
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 14
- 108091008874 T cell receptors Proteins 0.000 description 14
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 13
- 102000003945 NF-kappa B Human genes 0.000 description 12
- 230000004927 fusion Effects 0.000 description 12
- 208000008383 Wilms tumor Diseases 0.000 description 11
- 208000026448 Wilms tumor 1 Diseases 0.000 description 11
- 125000000539 amino acid group Chemical group 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 102000040945 Transcription factor Human genes 0.000 description 10
- 108091023040 Transcription factor Proteins 0.000 description 10
- 210000004899 c-terminal region Anatomy 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 230000004936 stimulating effect Effects 0.000 description 10
- 230000003993 interaction Effects 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 8
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 8
- 102100023132 Transcription factor Jun Human genes 0.000 description 8
- 239000006285 cell suspension Substances 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 238000003780 insertion Methods 0.000 description 8
- 230000037431 insertion Effects 0.000 description 8
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 8
- 230000035899 viability Effects 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 7
- 230000000890 antigenic effect Effects 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 6
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 6
- 102100027207 CD27 antigen Human genes 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 101000773083 Homo sapiens 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 6
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 6
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 6
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 description 6
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 description 6
- 101000829725 Homo sapiens Phospholipid hydroperoxide glutathione peroxidase Proteins 0.000 description 6
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 6
- 101001056234 Homo sapiens Sperm mitochondrial-associated cysteine-rich protein Proteins 0.000 description 6
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 6
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 6
- 241001529936 Murinae Species 0.000 description 6
- 108091005804 Peptidases Proteins 0.000 description 6
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 6
- 102100026503 Sperm mitochondrial-associated cysteine-rich protein Human genes 0.000 description 6
- 102100035721 Syndecan-1 Human genes 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 6
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 238000009169 immunotherapy Methods 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 6
- 238000003752 polymerase chain reaction Methods 0.000 description 6
- 238000001542 size-exclusion chromatography Methods 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 description 5
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 5
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 5
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 description 5
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 description 5
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 102000006240 membrane receptors Human genes 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000013074 reference sample Substances 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- HBZBAMXERPYTFS-SECBINFHSA-N (4S)-2-(6,7-dihydro-5H-pyrrolo[3,2-f][1,3]benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)[C@H]1CSC(=N1)c1nc2cc3CCNc3cc2s1 HBZBAMXERPYTFS-SECBINFHSA-N 0.000 description 4
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 4
- 108091008875 B cell receptors Proteins 0.000 description 4
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 description 4
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 4
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 4
- 230000009831 antigen interaction Effects 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 230000020411 cell activation Effects 0.000 description 4
- 239000006143 cell culture medium Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000003501 co-culture Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000004590 computer program Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 108010054624 red fluorescent protein Proteins 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000004114 suspension culture Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 3
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 3
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 3
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 3
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 102000034287 fluorescent proteins Human genes 0.000 description 3
- 108091006047 fluorescent proteins Proteins 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000007781 signaling event Effects 0.000 description 3
- 210000005253 yeast cell Anatomy 0.000 description 3
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 101100424688 Arabidopsis thaliana ESK1 gene Proteins 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 2
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 2
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 2
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 2
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 2
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 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
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 2
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 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
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 239000012505 Superdex™ Substances 0.000 description 2
- 101710156660 T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 108091005948 blue fluorescent proteins Proteins 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 2
- 239000005516 coenzyme A Substances 0.000 description 2
- 229940093530 coenzyme a Drugs 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 230000009827 complement-dependent cellular cytotoxicity Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 230000005750 disease progression 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
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- LIYGYAHYXQDGEP-UHFFFAOYSA-N firefly oxyluciferin Natural products Oc1csc(n1)-c1nc2ccc(O)cc2s1 LIYGYAHYXQDGEP-UHFFFAOYSA-N 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000001024 immunotherapeutic effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 2
- 238000010859 live-cell imaging Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000002101 lytic effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 230000003606 oligomerizing effect Effects 0.000 description 2
- JJVOROULKOMTKG-UHFFFAOYSA-N oxidized Photinus luciferin Chemical compound S1C2=CC(O)=CC=C2N=C1C1=NC(=O)CS1 JJVOROULKOMTKG-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000012146 running buffer Substances 0.000 description 2
- 229910052594 sapphire Inorganic materials 0.000 description 2
- 239000010980 sapphire Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- 101150026450 Act5C gene Proteins 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 102100030801 Elongation factor 1-alpha 1 Human genes 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102000018389 Exopeptidases Human genes 0.000 description 1
- 108010091443 Exopeptidases 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
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 102100028501 Galanin peptides Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000920078 Homo sapiens Elongation factor 1-alpha 1 Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 description 1
- 101001033293 Homo sapiens Interleukin enhancer-binding factor 3 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
- 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 101000621309 Homo sapiens Wilms tumor protein Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 102000008379 I-kappa B Proteins Human genes 0.000 description 1
- 108010021699 I-kappa B Proteins Proteins 0.000 description 1
- 102000001284 I-kappa-B kinase Human genes 0.000 description 1
- 108060006678 I-kappa-B kinase Proteins 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 102100039062 Interleukin enhancer-binding factor 3 Human genes 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 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 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 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
- 239000007993 MOPS buffer Substances 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- 101000713102 Mus musculus C-C motif chemokine 1 Proteins 0.000 description 1
- 101100338482 Mus musculus Hcst gene Proteins 0.000 description 1
- 101100179075 Mus musculus Icos gene Proteins 0.000 description 1
- 101100404853 Mus musculus Klrk1 gene Proteins 0.000 description 1
- 101100153537 Mus musculus Tnfrsf4 gene Proteins 0.000 description 1
- 101100427034 Mus musculus Tyrobp gene Proteins 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- 102000002673 NFATC Transcription Factors Human genes 0.000 description 1
- 108010018525 NFATC Transcription Factors Proteins 0.000 description 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000004695 Polyether sulfone Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 101150086694 SLC22A3 gene Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 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 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000028956 calcium-mediated signaling Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay 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
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 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
- 230000005284 excitation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000000198 fluorescence anisotropy Methods 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical compound OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 102000057266 human FCGR3A Human genes 0.000 description 1
- 102000053803 human HCST Human genes 0.000 description 1
- 102000043396 human ICOS Human genes 0.000 description 1
- 102000044042 human KLRK1 Human genes 0.000 description 1
- 102000050320 human TNFRSF4 Human genes 0.000 description 1
- 102000050327 human TNFRSF9 Human genes 0.000 description 1
- 102000045892 human TYROBP Human genes 0.000 description 1
- 102000046004 human WT1 Human genes 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 238000002847 impedance measurement Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000000111 isothermal titration calorimetry Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000002824 mRNA display Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-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
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229920006393 polyether sulfone Polymers 0.000 description 1
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000009258 tissue cross reactivity Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 125000001493 tyrosinyl group Chemical class [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000001429 visible spectrum Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B30/00—Methods of screening libraries
- C40B30/04—Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464424—CD20
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464452—Transcription factors, e.g. SOX or c-MYC
- A61K39/464453—Wilms tumor 1 [WT1]
-
- 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
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
-
- 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
- C07K16/3007—Carcino-embryonic Antigens
-
- 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
- C07K16/3038—Kidney, bladder
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5047—Cells of the immune system
- G01N33/505—Cells of the immune system involving T-cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/11—Antigen recognition domain
- A61K2239/13—Antibody-based
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/033—Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the internal surface of the plasma membrane, e.g. containing a myristoylation motif
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Toxicology (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Computational Biology (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
a) 試料をキメラ抗原受容体(CAR)発現レポーターT(CAR−T)細胞と接触させることであって、レポーターCAR−T細胞が、
i. 腫瘍細胞と特異的な相互作用ができるCARであって、応答要素へ作用可能に連結された、CARと、
ii. 応答要素の制御下にあるレポーター遺伝子とを含む、接触させること、および
b) 腫瘍細胞の存在を確立するためにレポーター遺伝子の発現を測定することによってT細胞の活性化を判定すること
を含む。
2表1において使用されるような小文字「b」が付いた「AbM」は、Oxford Molecularの「AbM」抗体モデリングソフトウェアによって定義されるようなCDRを指す。
a) 試料をキメラ抗原受容体(CAR)発現レポーターT(CAR−T)細胞と接触させることであって、レポーターCAR−T細胞が、
i. 腫瘍細胞と特異的な相互作用ができるCARであって、応答要素へ作用可能に連結された、CARと、
ii. 応答要素の制御下にあるレポーター遺伝子とを含む、接触させること、および
b) 腫瘍細胞の存在を確立するためにレポーター遺伝子の発現を測定することによって、T細胞の活性化を判定すること
を含む。
(a) YSWIN(配列番号1)の重鎖相補性決定領域(CDR H)1アミノ酸配列、
(b) RIFPGDGDTDYNGKFKG(配列番号2)のCDR H2アミノ酸配列、
(c) NVFDGYWLVY(配列番号3)のCDR H3アミノ酸配列と、
以下を含む軽鎖可変領域:
(d) RSSKSLLHSNGITYLY(配列番号4)の軽鎖(CDR L)1アミノ酸配列、
(e) QMSNLVS(配列番号5)のCDR L2アミノ酸配列、および
(f) AQNLELPYT(配列番号6)のCDR L3アミノ酸配列とを含む。
(a) EFGMN(配列番号36)の重鎖相補性決定領域(CDR H)1アミノ酸配列、
(b) WINTKTGEATYVEEFKG(配列番号37)のCDR H2アミノ酸配列、
(c) WDFAYYVEAMDY(配列番号38)のCDR H3アミノ酸配列と、
以下を含む軽鎖可変領域:
(d) KASAAVGTYVA(配列番号39)の軽鎖(CDR L)1アミノ酸配列、
(e) SASYRKR(配列番号40)のCDR L2アミノ酸配列、および
(f) HQYYTYPLFT(配列番号41)のCDR L3アミノ酸配列とを含む。
(a) GGTFSSYAIS(配列番号46)の重鎖相補性決定領域(CDR H)1アミノ酸配列、
(b) GIIPIFGTANYAQKFQG(配列番号47)のCDR H2アミノ酸配列、
(c) SIELWWGGFDY(配列番号48)およびGSYDLFSLDY(配列番号57)からなる群から選択されるCDR H3アミノ酸配列と、
以下を含む軽鎖可変領域:
(d) RASQSISSWLA(配列番号49)の軽鎖(CDR L)1アミノ酸配列、
(e) DASSLES(配列番号50)のCDR L2アミノ酸配列、および
(f) QQYEDYTT(配列番号51)およびQQYYDGIT(配列番号58)からなる群から選択されるCDR L3アミノ酸配列とを含む。
(g) GGTFSSYAIS(配列番号46)の重鎖相補性決定領域(CDR H)1アミノ酸配列、
(h) GIIPIFGTANYAQKFQG(配列番号47)のCDR H2アミノ酸配列、
(i) SIELWWGGFDY(配列番号48)のCDR H3アミノ酸配列と、
以下を含む軽鎖可変領域:
(j) RASQSISSWLA(配列番号49)の軽鎖(CDR L)1アミノ酸配列、
(k) DASSLES(配列番号50)のCDR L2アミノ酸配列、および
(l) QQYEDYTT(配列番号51)のCDR L3アミノ酸配列とを含む。
(a) GGTFSSYAIS(配列番号46)の重鎖相補性決定領域(CDR H)1アミノ酸配列、
(b) GIIPIFGTANYAQKFQG(配列番号47)のCDR H2アミノ酸配列、
(c) GSYDLFSLDY(配列番号57)のCDR H3アミノ酸配列と、
以下を含む軽鎖可変領域:
(d) RASQSISSWLA(配列番号49)の軽鎖(CDR L)1アミノ酸配列、
(e) DASSLES(配列番号50)のCDR L2アミノ酸配列、および
(f) QQYYDGIT(配列番号58)のCDR L3アミノ酸配列とを含む。
1.試料における腫瘍細胞の存在を判定するための診断アッセイであって、以下のステップ:
a) 試料をキメラ抗原受容体(CAR)発現レポーターT(CAR−T)細胞と接触させることであって、レポーターCAR−T細胞が、
i. 腫瘍細胞へ特異的な結合ができるCARであって、応答要素へ作用可能に連結された、CARと、
ii. 応答要素の制御下にあるレポーター遺伝子とを含む、接触させること、および
b) 腫瘍細胞の存在を確立するためにレポーター遺伝子の発現を測定することによってT細胞の活性化を判定すること
を含む、診断アッセイ。
c)レポーター遺伝子の発現を基準と比較すること
を追加で含む、実施形態1〜17のいずれか1つに記載の診断アッセイ。
d)基準の存在下でのレポーター遺伝子の発現と関連した患者試料の存在下でのレポーター遺伝子の発現が、事前に規定した閾値よりも高い場合、腫瘍細胞の存在を確立すること
を追加で含む、実施形態21に記載の診断アッセイ。
標準的な方法を使用して、Sambrook et al.,Molecular Cloning:A laboratory manual;Cold Spring Harbor Laboratory Press,Cold Spring Harbor,New York,1989において説明されるように、DNAを操作した。分子生物学的試薬は、製造元の説明書によって使用した。ヒト免疫グロブリンの軽鎖および重鎖のヌクレオチド配列に関する一般的な情報は、以下に与えられる:Kabat,E.A.et al.,(1991)Sequences of Proteins of Immunological Interest,第5版,NIH Publication No 91−3242に示されている。
DNA配列は、二本鎖配列決定によって決定した。
所望の遺伝子セグメントは、適切なテンプレートを使用したPCRによって生じたか、またはGeneart AG(Regensburg,Germany)によって、合成オリゴヌクレオチドおよびPCR産物から自動遺伝子合成によって合成した。単一の制限エンドヌクレアーゼ開裂部位に隣接する遺伝子セグメントを、標準的なクローニング/配列決定ベクター内へとクローニングした。プラスミドDNAを形質転換細菌から精製し、濃度をUV分光法によって測定した。サブクローニングした遺伝子フラグメントのDNA配列は、DNA配列決定によって確認した。遺伝子セグメントは、それぞれの発現ベクター内へのサブクローニングを可能にする適切な制限部位を用いて設計した。すべてのコンストラクトは、真核細胞における分泌のためのタンパク質を標的とするリーダー配列についてコードする5’末端DNA配列を用いて設計した。
タンパク質は、標準プロトコルに言及される、フィルタにかけた細胞培養物上清から精製した。簡潔に述べると、抗体を、Protein A Sepharoseカラム(GE healthcare)に適用し、PBSで洗浄した。抗体の溶離は、pH2.8で達成され、その後、試料を即時中和した。凝集したタンパク質は、PBS中での、または20mM ヒスチジン、150mM NaCl(pH6.0)中でのサイズ排除クロマトグラフィー(Superdex 200、GE Healthcare)によって、単量体抗体から分離した。単量体抗体画分をプールし、例えば、MILLIPORE Amicon Ultra(30分子量カットオフ)遠心分離濃縮器を用いて濃縮し、凍結させ、−20℃または−80℃で保存した。試料の一部を、例えば、SDS−PAGEおよびサイズ排除クロマトグラフィー(SEC)によるその後のタンパク質分析および分析による特徴づけに準備した。
NuPAGE(登録商標)Pre−Castゲルシステム(Invitrogen)を、製造元の説明書により使用した。特に、10%または4〜12%のNuPAGE(登録商標)Novex(登録商標)Bis−TRIS Pre−Castゲル(pH6.4)、およびNuPAGE(登録商標)MES(還元型ゲル、NuPAGE(登録商標)酸化防止剤ランニングバッファー助剤を添加)またはMOPS(非還元型ゲル)ランニングバッファーを使用した。
抗体の凝集およびオリゴマー状態を決定するためのサイズ排除クロマトグラフィー(SEC)は、HPLCクロマトグラフィーによって行った。簡潔に述べると、プロテインA精製抗体を、Agilent HPLC 1100システムの300mM NaCl、50mM KH2PO4/K2HPO4(pH7.5)におけるTosoh TSKgel G3000SWカラムに、またはDionex HPLC−Systemの2×PBSにおけるSuperdex 200カラム(GE Healthcare)に適用した。溶離したタンパク質をUV吸光度およびピーク面積の積分によって定量した。BioRad Gel Filtration Standard 151−1901を標準物質として供した。
個々の抗体は、HEK293−EBNA細胞に、ポリエチレンイミンを用いて哺乳動物発現ベクターを同時トランスフェクトすることによって作製した。細胞に、重鎖および軽鎖について対応する発現ベクターを1:1の比においてトランスフェクトした。
レンチウイルスベクターを作製するために、CARの正確な集合体のための個々のDNA配列を、構成的に活性のあるヒトサイトメガロウイルス前初期プロモーター(CMV)の下で、レンチウイルスポリヌクレオチドベクターにおいてインフレームでクローニングした。レトロウイルスベクターは、ウッドチャック肝炎ウイルス転写後調節要素(WPRE)、中央ポリプリントラクト(cPPT)要素、pUC複製起点、ならびに細菌における増殖および選択を容易にする抗生物質耐性についてコードする遺伝子を含有していた。
Claims (15)
- 試料における腫瘍細胞の存在を判定するための診断アッセイであって、以下のステップ:
a) 前記試料をキメラ抗原受容体(CAR)発現レポーターT(CAR−T)細胞と接触させることであって、前記レポーターCAR−T細胞が、
i. 前記腫瘍細胞へ特異的な結合ができるCARであって、応答要素へ作用可能に連結された、CARと、
ii. 前記応答要素の制御下にあるレポーター遺伝子とを含む、接触させること、および
b) 前記腫瘍細胞の存在を確立するために前記レポーター遺伝子の発現を測定することによってT細胞の活性化を判定すること
を含む、診断アッセイ。 - 前記CARが、腫瘍標的抗原に特異的に結合することができる標的抗原結合部分を含む、請求項1に記載の診断アッセイ。
- 前記標的抗原結合部分が、Fabフラグメントである、請求項2に記載の診断アッセイ。
- 前記レポーターCAR−T細胞が、Jurkat細胞である、請求項1〜3のいずれか1項に記載の診断アッセイ。
- 前記腫瘍標的抗原が、細胞表面抗原および/または細胞表面受容体である、請求項2〜4のいずれか1項に記載の診断アッセイ。
- 前記腫瘍標的抗原が、CD20、CD38、CD138、CEA、EGFR、FolR1、HER2、LeY、MCSP、STEAP1、TYRP1、およびWT1からなる群、またはこれらのフラグメントから選択される、請求項2または5に記載の診断アッセイ。
- 前記腫瘍標的抗原が、ヒト主要組織適合性複合体(MHC)の分子へ結合したペプチドである、請求項2〜6のいずれか1項に記載の診断アッセイ。
- 前記CARが、少なくとも1つの細胞内刺激シグナル伝達および/または同時刺激シグナル伝達ドメインを含む、請求項1〜7のいずれか1項に記載の診断アッセイ。
- 前記細胞内シグナル伝達および/または同時シグナル伝達ドメインの活性化が、前記応答要素の活性化をもたらす、請求項8に記載の診断アッセイ。
- 前記応答要素の活性化が、前記レポーター遺伝子の発現をもたらす、請求項1〜9のいずれか1項に記載の診断アッセイ。
- 前記応答要素が、NFAT経路、NF−κB経路またはAP−1経路の一部である、実施形態1〜10のいずれか1つに記載の診断アッセイ。
- 前記レポーター遺伝子が、発光タンパク質についてコードしている、実施形態1〜11のいずれか1つに記載の診断アッセイ。
- 前記レポーター遺伝子が、緑色蛍光タンパク質(GFP)またはルシフェラーゼについてコードしている、実施形態1〜12のいずれか1つに記載の診断アッセイ。
- 前記試料が、疾患に罹患している個体に由来する患者試料であり、特に前記疾患が、癌である、請求項1〜13のいずれか1項に記載の診断アッセイ。
- 抗腫瘍CAR−T細胞処置の有効性を予測するための方法であって、腫瘍を有する対象に由来の試料を与えることと、実施形態1〜15のいずれか1つに記載の診断アッセイによって前記レポーター遺伝子の発現を測定することによってT細胞の活性化を判定することとを含み、前記レポーター遺伝子の活性化が、前記対象へ適用される際の前記抗腫瘍CAR−T細胞処置の有効性を示す、方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18165601 | 2018-04-04 | ||
EP18165601.8 | 2018-04-04 | ||
PCT/EP2019/058214 WO2019192972A1 (en) | 2018-04-04 | 2019-04-02 | Diagnostic assays to detect tumor antigens in cancer patients |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2021520209A true JP2021520209A (ja) | 2021-08-19 |
Family
ID=61911391
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020554287A Pending JP2021520209A (ja) | 2018-04-04 | 2019-04-02 | 癌患者における腫瘍抗原を検出するための診断アッセイ |
Country Status (5)
Country | Link |
---|---|
US (1) | US20210025894A1 (ja) |
EP (1) | EP3775883A1 (ja) |
JP (1) | JP2021520209A (ja) |
CN (1) | CN112424601A (ja) |
WO (1) | WO2019192972A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2023538115A (ja) * | 2020-08-20 | 2023-09-06 | エー2 バイオセラピューティクス, インコーポレイテッド | Ceacam陽性がんを治療するための組成物及び方法 |
CN112433055A (zh) * | 2020-11-04 | 2021-03-02 | 上海药明生物技术有限公司 | 一种基于报告基因方法检测pvrig抗体的生物学活性的方法 |
CN113252894B (zh) * | 2021-07-07 | 2021-11-09 | 北京艺妙神州医药科技有限公司 | 一种检测CAR-T细胞scFv亲和力的方法 |
CN114262689A (zh) * | 2021-12-17 | 2022-04-01 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种快速检测cd19/cd20-car-t细胞活性的方法 |
WO2024057327A1 (en) * | 2022-09-14 | 2024-03-21 | B.G. Negev Technologies & Applications Ltd., At Ben-Gurion University | Reporter cells expressing chimeric polypeptides for use in determining presence and or activity of receptors associated with cancer and selecting treatment |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017513818A (ja) * | 2014-03-15 | 2017-06-01 | ノバルティス アーゲー | キメラ抗原受容体を使用する癌の処置 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990005144A1 (en) | 1988-11-11 | 1990-05-17 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
DE69334255D1 (de) | 1992-02-06 | 2009-02-12 | Novartis Vaccines & Diagnostic | Marker für Krebs und biosynthetisches Bindeprotein dafür |
CA2393869A1 (en) | 1999-12-15 | 2001-06-21 | Genetech,Inc. | Shotgun scanning, a combinatorial method for mapping functional protein epitopes |
JP4753578B2 (ja) | 2002-06-03 | 2011-08-24 | ジェネンテック, インコーポレイテッド | 合成抗体ファージライブラリー |
AU2004205631A1 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
US7785903B2 (en) | 2004-04-09 | 2010-08-31 | Genentech, Inc. | Variable domain library and uses |
EP1957531B1 (en) | 2005-11-07 | 2016-04-13 | Genentech, Inc. | Binding polypeptides with diversified and consensus vh/vl hypervariable sequences |
EP1973951A2 (en) | 2005-12-02 | 2008-10-01 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
JP2009536527A (ja) | 2006-05-09 | 2009-10-15 | ジェネンテック・インコーポレーテッド | 最適化されたスキャフォールドを備えた結合ポリペプチド |
CN100592373C (zh) | 2007-05-25 | 2010-02-24 | 群康科技(深圳)有限公司 | 液晶显示面板驱动装置及其驱动方法 |
WO2011028894A2 (en) | 2009-09-03 | 2011-03-10 | Blaine Laboratories, Inc. | Improved vibrating anesthesia device |
SG193023A1 (en) * | 2011-02-11 | 2013-10-30 | Sloan Kettering Inst Cancer | Hla-restricted, peptide-specific antigen binding proteins |
US20160152725A1 (en) * | 2014-02-25 | 2016-06-02 | Memorial Sloan-Kettering Cancer Center | Antigen-binding proteins specific for hla-a2-restricted wilms tumor 1 peptide |
-
2019
- 2019-04-02 JP JP2020554287A patent/JP2021520209A/ja active Pending
- 2019-04-02 CN CN201980027623.9A patent/CN112424601A/zh active Pending
- 2019-04-02 EP EP19713500.7A patent/EP3775883A1/en active Pending
- 2019-04-02 WO PCT/EP2019/058214 patent/WO2019192972A1/en unknown
-
2020
- 2020-10-02 US US17/062,270 patent/US20210025894A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017513818A (ja) * | 2014-03-15 | 2017-06-01 | ノバルティス アーゲー | キメラ抗原受容体を使用する癌の処置 |
Non-Patent Citations (3)
Title |
---|
"REPORTER GENE IMMUNOTHERAPY BIOASSAYS", JEN CHENG, PROMEGA CORPORATION, BEBPA BIOASSAY CONFERENCE S, vol. [online], healthdocbox.com, JPN6023001677, pages 1 - 16, ISSN: 0004971163 * |
JOURNAL OF IMMUNOLOGICAL METHODS, 2010, VOL.359, NO.1-2, PP.11-20, JPN6023001678, ISSN: 0004971164 * |
PROMEGAかわら版, プロメガ株式会社, 2017, 春号, PP.1-8, JPN6023001676, ISSN: 0004971162 * |
Also Published As
Publication number | Publication date |
---|---|
EP3775883A1 (en) | 2021-02-17 |
US20210025894A1 (en) | 2021-01-28 |
CN112424601A (zh) | 2021-02-26 |
WO2019192972A1 (en) | 2019-10-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7389424B2 (ja) | 抗gpc3抗体 | |
US11679127B2 (en) | Antigen binding receptors specific for mutated Fc domains | |
JP2021520209A (ja) | 癌患者における腫瘍抗原を検出するための診断アッセイ | |
US11851679B2 (en) | Method of assessing activity of recombinant antigen receptors | |
JP7394058B2 (ja) | 新規抗原結合部分の特異性試験のためのユニバーサルレポーター細胞アッセイ | |
CN112154157A (zh) | 抗ror1抗体及其用途 | |
US20200093861A1 (en) | Antigen binding receptor formats | |
US20210116455A1 (en) | Specificity assay for novel target antigen binding moieties | |
US11788205B2 (en) | Car-t cell assay for specificity test of novel antigen binding moieties | |
JP2023547447A (ja) | 改良型抗原結合受容体 | |
KR20210143096A (ko) | Cd22에 특이적인 항체 및 이의 용도 | |
US20210018509A1 (en) | Diagnostic assays to detect tumor antigens in cancer patients | |
JP2021528382A (ja) | 免疫エフェクター細胞を腫瘍細胞へ誘引する方法及び手段 | |
WO2022195241A1 (en) | Cd160 binding domain | |
CN113423720A (zh) | CAR文库和scFv的制造方法 | |
KR20210148823A (ko) | Cd22에 특이적인 항체 및 이의 용도 | |
KR20220122844A (ko) | Cd22에 특이적인 인간화 항체 및 이의 용도 | |
NZ795720A (en) | Anti-gpc3 antibody |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220330 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230120 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230124 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230324 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230607 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230711 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20230926 |