WO2021035446A1 - Récepteur de lymphocytes t pour la reconnaissance d'un peptide court d'antigène afp et séquence de codage de celui-ci - Google Patents
Récepteur de lymphocytes t pour la reconnaissance d'un peptide court d'antigène afp et séquence de codage de celui-ci Download PDFInfo
- Publication number
- WO2021035446A1 WO2021035446A1 PCT/CN2019/102359 CN2019102359W WO2021035446A1 WO 2021035446 A1 WO2021035446 A1 WO 2021035446A1 CN 2019102359 W CN2019102359 W CN 2019102359W WO 2021035446 A1 WO2021035446 A1 WO 2021035446A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tcr
- chain
- amino acid
- seq
- variable domain
- Prior art date
Links
- 108091008874 T cell receptors Proteins 0.000 title claims abstract description 319
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title claims abstract description 305
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 62
- 108091007433 antigens Proteins 0.000 title abstract description 40
- 102000036639 antigens Human genes 0.000 title abstract description 40
- 239000000427 antigen Substances 0.000 title abstract description 39
- 210000004027 cell Anatomy 0.000 claims abstract description 127
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 46
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 41
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 41
- 239000013598 vector Substances 0.000 claims abstract description 35
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 83
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 55
- 101000662902 Homo sapiens T cell receptor beta constant 2 Proteins 0.000 claims description 50
- 102100037298 T cell receptor beta constant 2 Human genes 0.000 claims description 50
- 239000002773 nucleotide Substances 0.000 claims description 50
- 125000003729 nucleotide group Chemical group 0.000 claims description 50
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 claims description 49
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 claims description 49
- 235000001014 amino acid Nutrition 0.000 claims description 49
- 150000001413 amino acids Chemical class 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 23
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 16
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 8
- 239000000833 heterodimer Substances 0.000 claims description 8
- 230000035772 mutation Effects 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 101150008942 J gene Proteins 0.000 claims description 6
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 6
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 6
- 230000002998 immunogenetic effect Effects 0.000 claims description 6
- 239000003550 marker Substances 0.000 claims description 6
- 210000000130 stem cell Anatomy 0.000 claims description 5
- 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 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 3
- 239000013603 viral vector Substances 0.000 claims description 3
- 210000000349 chromosome Anatomy 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 abstract description 36
- 230000027455 binding Effects 0.000 abstract description 6
- 230000002463 transducing effect Effects 0.000 abstract description 4
- 208000030062 persistent idiopathic facial pain Diseases 0.000 description 39
- 102000004196 processed proteins & peptides Human genes 0.000 description 24
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 23
- 239000012636 effector Substances 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 17
- 210000003000 inclusion body Anatomy 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 230000004913 activation Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 230000009258 tissue cross reactivity Effects 0.000 description 12
- 239000000872 buffer Substances 0.000 description 11
- 230000006870 function Effects 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 8
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 8
- 210000000612 antigen-presenting cell Anatomy 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 8
- 239000011534 wash buffer Substances 0.000 description 8
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 238000009169 immunotherapy Methods 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 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 6
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 230000003915 cell function Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000004153 renaturation Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000011510 Elispot assay Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- 102000001253 Protein Kinase Human genes 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 238000005349 anion exchange Methods 0.000 description 3
- 230000006287 biotinylation Effects 0.000 description 3
- 238000007413 biotinylation Methods 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 108060006633 protein kinase Proteins 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 101710130607 Valacyclovir hydrolase Proteins 0.000 description 2
- 102100025139 Valacyclovir hydrolase Human genes 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 2
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 2
- 229940099500 cystamine Drugs 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 239000012154 double-distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 230000008054 signal transmission Effects 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- PMUNIMVZCACZBB-UHFFFAOYSA-N 2-hydroxyethylazanium;chloride Chemical compound Cl.NCCO PMUNIMVZCACZBB-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 101100172874 Caenorhabditis elegans sec-3 gene Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 235000000638 D-biotin Nutrition 0.000 description 1
- 239000011665 D-biotin Substances 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010053070 Glutathione Disulfide Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 239000012506 Sephacryl® Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 241000703392 Tribec virus Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 101150063416 add gene Proteins 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000012197 amplification kit Methods 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000007998 bicine buffer Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 238000010370 cell cloning Methods 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000010580 coupled enzyme reaction Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000001094 effect on targets Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000011034 membrane dialysis Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000010223 real-time analysis Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 210000001325 yolk sac Anatomy 0.000 description 1
Images
Classifications
-
- 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
- A61K39/46448—Cancer antigens from embryonic or fetal origin
- A61K39/464481—Alpha-feto protein
-
- 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
- A61K39/4632—T-cell receptors [TCR]; antibody T-cell receptor constructs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/867—Retroviral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gynecology & Obstetrics (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Pregnancy & Childbirth (AREA)
- Reproductive Health (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
La présente invention concerne un récepteur de lymphocytes T (TCR) capable de se lier de manière spécifique à un peptide court FMNKFIYEI dérivé d'un antigène AFP, le peptide court FMNKFIYEI d'antigène pouvant former un complexe avec HLA A0201 et être présenté au niveau de la surface cellulaire conjointement avec celui-ci. La présente invention concerne également une molécule d'acide nucléique codant pour le TCR et un vecteur comprenant la molécule d'acide nucléique. La présente invention concerne par ailleurs une cellule de transduction du TCR selon la présente invention.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2019/102359 WO2021035446A1 (fr) | 2019-08-23 | 2019-08-23 | Récepteur de lymphocytes t pour la reconnaissance d'un peptide court d'antigène afp et séquence de codage de celui-ci |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2019/102359 WO2021035446A1 (fr) | 2019-08-23 | 2019-08-23 | Récepteur de lymphocytes t pour la reconnaissance d'un peptide court d'antigène afp et séquence de codage de celui-ci |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2021035446A1 true WO2021035446A1 (fr) | 2021-03-04 |
Family
ID=74684813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2019/102359 WO2021035446A1 (fr) | 2019-08-23 | 2019-08-23 | Récepteur de lymphocytes t pour la reconnaissance d'un peptide court d'antigène afp et séquence de codage de celui-ci |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2021035446A1 (fr) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104087592A (zh) * | 2014-05-13 | 2014-10-08 | 天津医科大学总医院 | Afp158-166特异性tcr基因及其转基因t细胞及体外增殖方法及用途 |
| JP2017081836A (ja) * | 2015-10-23 | 2017-05-18 | 国立大学法人金沢大学 | 細胞傷害性ｔ細胞の作製方法 |
| CN109575121A (zh) * | 2017-09-28 | 2019-04-05 | 广东香雪精准医疗技术有限公司 | 识别afp抗原短肽的t细胞受体 |
-
2019
- 2019-08-23 WO PCT/CN2019/102359 patent/WO2021035446A1/fr active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104087592A (zh) * | 2014-05-13 | 2014-10-08 | 天津医科大学总医院 | Afp158-166特异性tcr基因及其转基因t细胞及体外增殖方法及用途 |
| JP2017081836A (ja) * | 2015-10-23 | 2017-05-18 | 国立大学法人金沢大学 | 細胞傷害性ｔ細胞の作製方法 |
| CN109575121A (zh) * | 2017-09-28 | 2019-04-05 | 广东香雪精准医疗技术有限公司 | 识别afp抗原短肽的t细胞受体 |
Non-Patent Citations (1)
| Title |
|---|
| ALEKSIC, M. ET AL.: "Different affinity windows for virus and cancer—specific T—cell receptors: Implications for therapeutic strategies", EUR.J. IMMUNOL., vol. 42, no. 12, 31 December 2012 (2012-12-31), XP055683815, DOI: 20200731180838A * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7452880B2 (ja) | Ｓｓｘ２抗原を識別するｔ細胞受容体 | |
| WO2021068938A1 (fr) | Récepteur de lymphocytes t reconnaissant une mutation kras et séquence de codage associée | |
| WO2017076308A1 (fr) | Tcr pour identifier un oligopeptide d'antigènes ny-eso-1 | |
| CN106749620B (zh) | 识别mage-a1抗原短肽的t细胞受体 | |
| CN106831978B (zh) | 识别prame抗原的t细胞受体 | |
| JP7429455B2 (ja) | Ａｆｐ抗原を識別するｔ細胞受容体 | |
| WO2021170115A1 (fr) | Récepteur de lymphocytes t reconnaissant le hpv | |
| WO2021022447A1 (fr) | Récepteur de slymphocytes t capable de reconnaître un peptide court dérivé d'un antigène afp | |
| CN109575121B (zh) | 识别afp抗原短肽的t细胞受体 | |
| WO2021016887A1 (fr) | Récepteur de lymphocytes t reconnaissant le peptide court de l'antigène ssx2 | |
| WO2021170116A1 (fr) | Récepteur de lymphocytes t reconnaissant l'afp | |
| WO2021170117A1 (fr) | Récepteur de lymphocytes t reconnaissant un peptide court d'antigène afp et séquence de codage de celui-ci | |
| WO2021139698A1 (fr) | Récepteur de lymphocytes t pour l'identification d'un antigène de hpv et séquence codante associée | |
| WO2016177195A1 (fr) | Récepteur des cellules t permettant de reconnaître le polypeptide à chaîne courte de l'antigène rhamm | |
| WO2021139699A1 (fr) | Récepteur de lymphocytes t pour la reconnaissance de l'afp et séquence codante associée | |
| CN110577590B (zh) | 一种识别afp抗原的tcr及其编码核酸 | |
| WO2021035446A1 (fr) | Récepteur de lymphocytes t pour la reconnaissance d'un peptide court d'antigène afp et séquence de codage de celui-ci | |
| WO2022262835A1 (fr) | Tcr pour identifier un antigène afp et séquence codant pour celui-ci | |
| WO2022206861A1 (fr) | Récepteur de lymphocytes t pour l'identification d'afp | |
| WO2022166904A1 (fr) | Récepteur de lymphocytes t pour identifier l'hpv | |
| CN110272483B (zh) | 识别sage1抗原短肽的t细胞受体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 19943839 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 19943839 Country of ref document: EP Kind code of ref document: A1 |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 19943839 Country of ref document: EP Kind code of ref document: A1 |
|
| 32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 22.09.2022) |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 19943839 Country of ref document: EP Kind code of ref document: A1 |