JP7116126B6 - 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) - Google Patents
形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) Download PDFInfo
- Publication number
- JP7116126B6 JP7116126B6 JP2020139041A JP2020139041A JP7116126B6 JP 7116126 B6 JP7116126 B6 JP 7116126B6 JP 2020139041 A JP2020139041 A JP 2020139041A JP 2020139041 A JP2020139041 A JP 2020139041A JP 7116126 B6 JP7116126 B6 JP 7116126B6
- Authority
- JP
- Japan
- Prior art keywords
- egfr
- cells
- nucleic acid
- acid molecule
- egfrt
- 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.)
- Active
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims description 100
- 102000001301 EGF receptor Human genes 0.000 title claims description 35
- 108060006698 EGF receptor Proteins 0.000 title claims description 33
- 210000004027 cell Anatomy 0.000 claims description 136
- 238000000034 method Methods 0.000 claims description 43
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 102000039446 nucleic acids Human genes 0.000 claims description 21
- 150000007523 nucleic acids Chemical class 0.000 claims description 21
- 230000011664 signaling Effects 0.000 claims description 15
- 239000013598 vector Substances 0.000 claims description 15
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 14
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 14
- 239000002773 nucleotide Substances 0.000 claims description 14
- 125000003729 nucleotide group Chemical group 0.000 claims description 14
- 150000001413 amino acids Chemical group 0.000 claims description 13
- 239000000427 antigen Substances 0.000 claims description 13
- 108091007433 antigens Proteins 0.000 claims description 13
- 102000036639 antigens Human genes 0.000 claims description 13
- 239000003446 ligand Substances 0.000 claims description 11
- 239000003550 marker Substances 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 6
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 3
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 3
- 230000032258 transport Effects 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims 13
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical class C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000000779 depleting effect Effects 0.000 claims 1
- 108010034265 Vascular Endothelial Growth Factor Receptors Proteins 0.000 description 110
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 109
- 229960005395 cetuximab Drugs 0.000 description 44
- 108090000623 proteins and genes Proteins 0.000 description 25
- 108020003175 receptors Proteins 0.000 description 17
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 16
- 230000001745 anti-biotin effect Effects 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 239000011651 chromium Substances 0.000 description 14
- 238000000684 flow cytometry Methods 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 11
- 239000012636 effector Substances 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 229960004641 rituximab Drugs 0.000 description 9
- 230000009261 transgenic effect Effects 0.000 description 9
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 8
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000011325 microbead Substances 0.000 description 8
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 7
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 7
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 7
- 239000011324 bead Substances 0.000 description 7
- 229910052804 chromium Inorganic materials 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 238000009169 immunotherapy Methods 0.000 description 7
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 6
- 230000001472 cytotoxic effect Effects 0.000 description 6
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 6
- 229960000951 mycophenolic acid Drugs 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 241000713666 Lentivirus Species 0.000 description 5
- 108010090804 Streptavidin Proteins 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 5
- 210000002865 immune cell Anatomy 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 102220003351 rs387906411 Human genes 0.000 description 5
- 238000010361 transduction Methods 0.000 description 5
- 230000026683 transduction Effects 0.000 description 5
- 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 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102100033467 L-selectin Human genes 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940082789 erbitux Drugs 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 108010044426 integrins Proteins 0.000 description 4
- 102000006495 integrins Human genes 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 229960003989 tocilizumab Drugs 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001076642 Homo sapiens Inosine-5'-monophosphate dehydrogenase 2 Proteins 0.000 description 3
- 102100025891 Inosine-5'-monophosphate dehydrogenase 2 Human genes 0.000 description 3
- 102100025390 Integrin beta-2 Human genes 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 108091081021 Sense strand Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229950008001 matuzumab Drugs 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229960000513 necitumumab Drugs 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 229960001972 panitumumab Drugs 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 150000003668 tyrosines Chemical class 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
- 102100032937 CD40 ligand Human genes 0.000 description 2
- 108091008048 CMVpp65 Proteins 0.000 description 2
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 2
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 2
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 2
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 2
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000755649 Midgee Species 0.000 description 2
- 101001033610 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 108020005091 Replication Origin Proteins 0.000 description 2
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- ZUPXXZAVUHFCNV-UHFFFAOYSA-N [[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [5-(3-carbamoyl-4h-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate;potassium Chemical compound [K].C1=CCC(C(=O)N)=CN1C1C(O)C(O)C(COP(O)(=O)OP(O)(=O)OCC2C(C(O)C(O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ZUPXXZAVUHFCNV-UHFFFAOYSA-N 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229950006647 cixutumumab Drugs 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 229960000520 diphenhydramine Drugs 0.000 description 2
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 229950002142 minretumomab Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 229950007217 tremelimumab Drugs 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- FOIAQXXUVRINCI-LBAQZLPGSA-N (2S)-2-amino-6-[[4-[2-[bis(carboxymethyl)amino]-3-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]propyl]phenyl]carbamothioylamino]hexanoic acid Chemical compound N[C@@H](CCCCNC(=S)Nc1ccc(CC(CN(CCN(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)cc1)C(O)=O FOIAQXXUVRINCI-LBAQZLPGSA-N 0.000 description 1
- ZMEWRPBAQVSBBB-GOTSBHOMSA-N (2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]hexanoic acid Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 ZMEWRPBAQVSBBB-GOTSBHOMSA-N 0.000 description 1
- 238000010176 18-FDG-positron emission tomography Methods 0.000 description 1
- ZCXUVYAZINUVJD-AHXZWLDOSA-N 2-deoxy-2-((18)F)fluoro-alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H]([18F])[C@@H](O)[C@@H]1O ZCXUVYAZINUVJD-AHXZWLDOSA-N 0.000 description 1
- 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 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 102100032412 Basigin Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 210000003771 C cell Anatomy 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 108010005327 CD19-specific chimeric antigen receptor Proteins 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039622 Granulocyte colony-stimulating factor receptor Human genes 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 101000798441 Homo sapiens Basigin Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 description 1
- 101000746364 Homo sapiens Granulocyte colony-stimulating factor receptor Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055157 Homo sapiens Interleukin-15 Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 1
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 1
- 101000801433 Homo sapiens Trophoblast glycoprotein Proteins 0.000 description 1
- 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 1
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102000001617 Interferon Receptors Human genes 0.000 description 1
- 108010054267 Interferon Receptors Proteins 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 102100023123 Mucin-16 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100118551 Mus musculus Egfr gene Proteins 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 238000012879 PET imaging Methods 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 102100022019 Pregnancy-specific beta-1-glycoprotein 2 Human genes 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 102100029198 SLAM family member 7 Human genes 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 102100037116 Transcription elongation factor 1 homolog Human genes 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 1
- 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- XYVNHPYNSPGYLI-UUOKFMHZSA-N [(2r,3s,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-4-hydroxy-2-(phosphonooxymethyl)oxolan-3-yl] dihydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O XYVNHPYNSPGYLI-UUOKFMHZSA-N 0.000 description 1
- 229950005186 abagovomab Drugs 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 229950009084 adecatumumab Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229950009106 altumomab Drugs 0.000 description 1
- 229950006061 anatumomab mafenatox Drugs 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229950003145 apolizumab Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 229950005725 arcitumomab Drugs 0.000 description 1
- 229950002882 aselizumab Drugs 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- 229950003269 bectumomab Drugs 0.000 description 1
- 229950000321 benralizumab Drugs 0.000 description 1
- 229950010559 besilesomab Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 229960005522 bivatuzumab mertansine Drugs 0.000 description 1
- 229960003008 blinatumomab Drugs 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 229950007296 cantuzumab mertansine Drugs 0.000 description 1
- 229940034605 capromab pendetide Drugs 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 229950006754 cedelizumab Drugs 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229950001357 celmoleukin Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229950002334 clenoliximab Drugs 0.000 description 1
- 229950002595 clivatuzumab tetraxetan Drugs 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 108010021994 cytomegalovirus matrix protein 65kDa Proteins 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 229950007409 dacetuzumab Drugs 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 229960002204 daratumumab Drugs 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 229950008962 detumomab Drugs 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229950000006 ecromeximab Drugs 0.000 description 1
- 229960001776 edrecolomab Drugs 0.000 description 1
- 229960000284 efalizumab Drugs 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229960004137 elotuzumab Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229950000565 enlimomab pegol Drugs 0.000 description 1
- 229950006414 epitumomab cituxetan Drugs 0.000 description 1
- 229950009760 epratuzumab Drugs 0.000 description 1
- 229950004292 erlizumab Drugs 0.000 description 1
- 229950008579 ertumaxomab Drugs 0.000 description 1
- 229950009569 etaracizumab Drugs 0.000 description 1
- 229950001488 faralimomab Drugs 0.000 description 1
- 229950009929 farletuzumab Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 229950008085 figitumumab Drugs 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 102000006815 folate receptor Human genes 0.000 description 1
- 108020005243 folate receptor Proteins 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229950001109 galiximab Drugs 0.000 description 1
- 229950004792 gavilimomab Drugs 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229950009672 glembatumumab vedotin Drugs 0.000 description 1
- 229940126613 gomiliximab Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000045108 human EGFR Human genes 0.000 description 1
- 102000056003 human IL15 Human genes 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229950010245 ibalizumab Drugs 0.000 description 1
- 229950002200 igovomab Drugs 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000003331 infrared imaging Methods 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229950007937 inolimomab Drugs 0.000 description 1
- 229950004101 inotuzumab ozogamicin Drugs 0.000 description 1
- 230000035990 intercellular signaling Effects 0.000 description 1
- 229950001014 intetumumab Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 229950010939 iratumumab Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 229950010828 keliximab Drugs 0.000 description 1
- 229950000518 labetuzumab Drugs 0.000 description 1
- 229940121292 leronlimab Drugs 0.000 description 1
- 229950002884 lexatumumab Drugs 0.000 description 1
- 229950002950 lintuzumab Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229950004563 lucatumumab Drugs 0.000 description 1
- 229950000128 lumiliximab Drugs 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229950001869 mapatumumab Drugs 0.000 description 1
- 229950008083 maslimomab Drugs 0.000 description 1
- 229950003734 milatuzumab Drugs 0.000 description 1
- 229950003063 mitumomab Drugs 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000001400 myeloablative effect Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229950009793 naptumomab estafenatox Drugs 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000007514 neuronal growth Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229950010203 nimotuzumab Drugs 0.000 description 1
- 229960003347 obinutuzumab Drugs 0.000 description 1
- 229950005751 ocrelizumab Drugs 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 229950010465 odulimomab Drugs 0.000 description 1
- 229960002450 ofatumumab Drugs 0.000 description 1
- 229950008516 olaratumab Drugs 0.000 description 1
- 229950009057 oportuzumab monatox Drugs 0.000 description 1
- 229950007283 oregovomab Drugs 0.000 description 1
- 229950002610 otelixizumab Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000012335 pathological evaluation Methods 0.000 description 1
- 229960005570 pemtumomab Drugs 0.000 description 1
- 229950011098 pendetide Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940067082 pentetate Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 238000009101 premedication Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229950003700 priliximab Drugs 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 108010056030 retronectin Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229950001808 robatumumab Drugs 0.000 description 1
- 229950009092 rovelizumab Drugs 0.000 description 1
- 229950005374 ruplizumab Drugs 0.000 description 1
- 229950007308 satumomab Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229950003804 siplizumab Drugs 0.000 description 1
- JJGWLCLUQNFDIS-GTSONSFRSA-M sodium;1-[6-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCNC(=O)CCCC[C@H]1[C@H]2NC(=O)N[C@H]2CS1 JJGWLCLUQNFDIS-GTSONSFRSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229950006551 sontuzumab Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011397 standard salvage chemotherapy Methods 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229950001072 tadocizumab Drugs 0.000 description 1
- 101150047061 tag-72 gene Proteins 0.000 description 1
- 229950001603 taplitumomab paptox Drugs 0.000 description 1
- 229950000301 teneliximab Drugs 0.000 description 1
- 229950010127 teplizumab Drugs 0.000 description 1
- 229950004742 tigatuzumab Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229950001802 toralizumab Drugs 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960004914 vedolizumab Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229950000815 veltuzumab Drugs 0.000 description 1
- 229950004393 visilizumab Drugs 0.000 description 1
- 229950003511 votumumab Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229950008250 zalutumumab Drugs 0.000 description 1
- 229950009002 zanolimumab Drugs 0.000 description 1
- 229950009083 ziralimumab Drugs 0.000 description 1
- 229950001346 zolimomab aritox Drugs 0.000 description 1
Images
Classifications
-
- 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
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- 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
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4634—Antigenic peptides; polypeptides
-
- 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
- A61K39/464411—Immunoglobulin superfamily
- A61K39/464412—CD19 or B4
-
- 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
- A61K39/464838—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- 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
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
-
- 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
- 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
- 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
- C12N2510/00—Genetically modified cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/10—Protein-tyrosine kinases (2.7.10)
- C12Y207/10001—Receptor protein-tyrosine kinase (2.7.10.1)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Developmental Biology & Embryology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
材料及び方法
抗体及びフローサイトメトリ
FITC-、PE-及びPerCP-共役アイソタイプコントロール、PerCP-共役抗CD8、FITC共役抗CD4、PE-共役抗IFNγ、PerCP-共役抗CD45及びPE-共役ストレプトアビジンは、BD Biosciences(San Jose、CA)から入手した。ビオチン化抗Fcは、Jackson ImmunoResearch Laboratories、Inc.(Westgrove、PA)から購入した。PE-共役抗ビオチンはMiltenyi Biotec(Auburn、CA)から購入した。ビオチン化EGFはMolecular Probes(R)Invitrogen(Carlsbad、CA)から入手した。PE-共役抗EGFRはAbeam Inc.(Cambridge、MA)から購入した。全ての抗体及びビオチンEGFは製造者の指示書に沿って使用した。フローサイトメトリデータ取得は、FACScalibur(BD Biosciences)で行い、分析の領域での細胞パーセントは、 FCS Express V3(De Novo Software、LosAngeles、CA)を用いて計算した。
特に記載されない限り、全ての細胞は、2mMのL-グルタミン(Irvine Scientific)、25mMのN-2-ヒドロキシエチルピペラジン-N’-2-エタンスルホン酸(HEPES、Irvine Scientific)、100 U/mLのペニシリン、0.1mg/mLのストレプトマイシン(Irvine Scientific)、及び10%加熱-不活性化ウシ胎児血清(FCS、 Hyclone、Logan、UT)を加えたRPMI1640 (Irvine Scientific、 Santa Ana、CA)中(以下培養培地(CM)とする)で保存された。
細胞(107まで)を、ホスファターゼインヒビタカクテルII80μLを含む1%トリトン-X溶解バッファ(Sigma-Aldrich Corp.、St.Louis、MO)(インヒビタ対バッファ容積比1:20)で溶解させた。50μgのタンパク質をそれぞれのレーンに載せ、ウェスタンブロットを、プローブとしてホスフォ-EGFレセプタ抗体サンプルキット(Cell Signaling Technology、Inc.、Danvers、MA)を用いて行い、続いて山羊抗ウサギ抗体(LI-COR、Lincoln、NE)共役IRDye(TM)680CW又は800CWと、同様に抗ベータアクチン抗体 (LI-COR)共役IRDye(TM) 800を、製造者の指示書に沿って用いて行った。ブロットはOdyssey Infrared Imaging System(LI-COR)で画像化させた。
T細胞の細胞溶解活性が、4時間クロム遊離アッセイ(CRA)で決定された。ここでエフェクタ細胞は5x103のCr51ラベル化ターゲットT細胞(Na2 51CrO4;5mCi/ml);Amersham Pharmacia、Piscataway、NJ)を含むV底96ウェルマイクロプレートの3重ウェルに播種され、5%CO2中37℃で種々のE:T比で200μLのCM中で4時間インキュベートされた。プレートを遠心分離し、上澄みの100μlをそれぞれのウェルから除いてγカウンタ(Packard Cobra II、 Downer’s Grove、IL)を用いて遊離クロムを評価した。 特定溶解パーセントは次のように計算された:100x(実験的遊離-自発的遊離)/(最大遊離-自発的遊離)。最大遊離は、2%SDSで溶解されたラベル化標的を含むウェルのCr含有量の測定から決定された。
T細胞移植のために、6から10週齢NOD/ScidIL-2RγCnullマウスに、107T細胞(細胞株C)が0日に静脈内に注射された。2x107照射(8000ラド)NSO-GFP:IMPDH2-IL15(IL2ss)_pcDNA3.1(+)(cJ02096)細胞が、インビボでヒトIL-15の系統的供給を与えるために0日で週3回腹腔内投与される。骨髄を安楽死させた動物から採取しフローサイトメトリで分析した。抗体依存性細胞傷害アッセイは、EGFRt+T細胞に対するセツキシマブの活性を決定することで実施される。
EGFRt発現T細胞の免疫的磁気選別
トランケートヒトEGFR(EGFRt)は、全長EGFRの膜間ドメインと細胞外ドメインIII及びIVのみを含み、免疫的磁気選別と適合して非免疫的磁気選択エピトープとして調製された。図1の分子モデルに示されるように、EGFRtはセツキシマブにより結合され得る機能を保持するが、細胞間ドメインの欠失により全てのシグナル系を欠いている。さらに、これはEGF結合に必要なN末端ドメインを欠いている。
EGFRtが不活性であることを確認するために、EGFRリン酸化についてのウェスタン免疫ブロット分析を、EGFRr選別T細胞でEGF又はセツキシマブで培養後に行った。予想の通り、セツキシマブはバックグラウンド以上のEGFRリン酸化を誘導せず、EGFR+細胞株A431でさえもそうであった(図3A)。さらに、A431細胞で見られたこととは対照的に、EGFとコインキュベート後の細胞株Aの溶解物でもリン酸化は見られなかった。実際、ビオチン化EGFを用いてフローサイトメトリ分析では、EGFはEGFRt選別T細胞には結合せず(図3B)、これはそのN、末端をトランケートされていることによると予想される。これらのEGFRt+T細胞はまた、セツキシマブとは異なる他の抗EGFR抗体でも認識されなかった。
AutoMACS(TM)分離の直後、選別されたT細胞は、OKT3、照射PBMCフィーダー及びLCL、IL-2及びOL-5でのREM刺激の後12日以内に30倍以上に増殖した(図4A)。得られた増殖EGFRt+T細胞のフローサイトメトリ分析はさらに、それらがCD19CAR及びCD8、TCR、CD3、パーホリン、グランザイムなどのT細胞マーカーを発現していることが確認された(図4B)。さらに、これらのEGFRt選別細胞株のCD19CARによる細胞活性は、CD19発現腫瘍ターゲットを用いて遊離クロムアッセにより明らかである(図4C)。細胞株Eとその非選別又は「親の」細胞株のCD19特異的反応性の直接比較は、EGFRt選別において強化されたCD19CAR介在細胞傷害性があることを示す。さらに、CMV特的TCM-誘導CD19CAR+EGFRt+細胞株B細胞はまた、ターゲット発現CMV-pp65抗原に対するこれらの外因性T細胞レセプタを介して細胞傷害性を示す。
インビボでの移植T細胞を検出する可能性を試験するために、CD19CAR+EGFRt+細胞株Cで移植させたマウスから集めた骨髄細胞が、ビオチン化セツキシマブを用いてフローサイトメトリで分析された(図5)。T細胞を受けていないコントロールマウスは、マウスEGFRに対してある程度のセツキシマブの交差反応があることを示した。従って、移植細胞株C細胞の検出を可能とするためには、ヒトCD45及びEGFRtの両方の二重染色が必要であることが決定された。細胞はまた、免疫組織化学を用いて、生検材料をスクリーニングするための可能性を決定するために分析され得る。
セツキシマブはEGFR発現細胞を、抗体依存性細胞傷害(ADCC)を介して溶解することが知られていることから、EGFRt+T細胞に対するセツキシマブの活性を決定するためにアッセイを行った(図6)。51Crラベル化細胞株A細胞をターゲットとし、新たに単離したヒトPBMCをエフェクタとして用いて、セツキシマブは、CD20特異的ヒト化mAbリツキサン(Rituxan)を用いた場合を超える有意にクロム遊離を介在することが見出された。
高リスクの中間悪性度B細胞リンパ腫を持つ大人の対象体は、自己骨髄破壊的幹細胞移植の候補者であり、適合的に転移された自己TCM-誘導CD19R+CD8+EGFRt+T細胞移植物による移植後免疫治療を受け得る。
それぞれの患者から集めた白血球分離物が、TCM選別され、医療グレードのCD19CAR-T2A-EGFRt_epHIV7で遺伝子組換えされ、その後選別され閉鎖系内でEGFRt+T細胞の増殖を行う。得られた細胞物は品質管理試験(殺菌及び腫瘍特異的細胞傷害性試験)を経て、凍結保存される。一方で、白血球除去輸血後に、研究参加者は、腫瘍低減化学療法及びG-CSFとの自動HSC収集のための動員とともに標準のサルベージ化学的治療を開始する。EGFRt選別、CD19特異的T細胞はまた、通常のCD20+(CD19+)B細胞もターゲットとするものであり、遺伝子改変CTLを受ける際に患者の炎症応答を低減させ、およびまた直ぐに目標のリンパ球へ注射されたT細胞を増加させるために、リツキシマブ(TM)を用いて最初B細胞数を低減させることができる。さらに、リツキシマブ(TM)は、遺伝子組換えT細胞に対してホルモン性免疫応答を遅らせる可能性がある。リツキシマブ(TM)が、前記サルベージ/プライミング治療戦略の一部として与えられない場合には、研究参加者はリツキシマブ(TM)(キメラ抗CD20抗体)を375mg/m2で計画された自動HSCT手順の4週間内に1回の静脈注射を受けることができる。リツキシマブ注射は標準方法で実行され得る。これにはジフェンヒドラミン及びアセトアミノフェン及びヒドロコルチゾンの前投与が含まれる。HSCT後の2日目と3日目で、自己凍結保存CD19R+CD8+EGFRt+T細胞物が輸送され、患者の側で解凍される。研究参加者はT細胞注射の少なくとも30分前に、15mg/kgのアセトアミノフェン経口(最大650mg)及び15~1mg/kg静脈注射(最大投与50mg)のジフェンヒドラミンが前投与され得る。臨床及び実験室の相互関連フォローアップ研究は、医師の裁量で実施され得る。これには、CD19発現リンパ球細胞及び/又は適合性遺伝子組換えT細胞の適量的RT-PCR研究;FDG-PET及び/又はCTスキャン;疾患特異的病理学的評価のための骨髄検査;リンパ節生検;及び/又は長期間フォローアップであり、FDAのBiologic Response Modifiers Advisory Committeeにより設定されたガイドラインの沿った遺伝子組み換え研究に適用されるものが含まれる。図10は本発明に係る物及び方法の臨床試験のための可能なスキームを与える。
1 . Berger、C、Flowers、ME、Warren、EH、and Riddell、SR(2006).Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation.Blood 107:2294-302.
2. Tey、SK、Dotti、G、Rooney、CM、Heslop、HE、and Brenner、MK(2007).Inducible caspase 9 suicide gene to improve the safety of allodepleted T cells after haploidentical stem cell transplantation.Biol Blood Marrow Transplant 13:913-24.
3. Fehse、B、Richters、A、Putimtseva-Scharf、K、Klump、H、Li、Z、Ostertag、W、 et al.(2000).CD34 splice variant:an attractive marker for selection of gene-modified cells.Mol Ther V.448-56.
4. Gaines、P、and Wojchowski、DM(1999).plRES-CD4t、a dicistronic expression vector for MACS-orFACS-based selection of transfected cells.Biotechniques26:683-8.
5. Fehse、B、Uhde、A、Fehse、N、Eckert、HG、Clausen、J、Ruger、R、et al.(1997).Selective immunoaffinity-based enrichment of CD34+ cells transduced with retroviral vectors containing an intracytoplasmatically truncated version of the human low-affinity nerve growth factor receptor(deltaLNGFR)gene.Hum Gene Ther 8:1815-24.
6. Lemoine、FM、Mesel-Lemoine、M、Cherai、M、Gallot、G、Vie、H、Leclercq、V、et al.(2004).Efficient transduction and selection of human T-lymphocytes with bicistronic Thy1/HSV1-TK retroviral vector produced by a human packaging cell line.J Gene Med 6:374-86.
7. Li、S、Schmitz、KR、Jeffrey、PD、Wiltzius、JJ、Kussie、P、and Ferguson、KM(2005).Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.Cancer Cell 7:301-11.
8. Dawson、JP、Berger、MB、Lin、CC、Schlessinger、J、Lemmon、MA、 and Ferguson、KM(2005).Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface.Mol Cell Biol 25:7734-42.
9. Lange、C、Li、Z、Fang、L、Baum、C、and Fehse、B(2007).CD34 modulates the trafficking behavior of hematopoietic cells in vivo. Stem Cells Dev 16:297-304.
10. Kowolik、CM、Topp、MS、Gonzalez、S、Pfeiffer、T、Olivares、S、Gonzalez、N、et al.(2006).CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells.Cancer Res 66:10995-1004.
11. Szymczak、AL、Workman、CJ、Wang、Y、Vignali、KM、Dilioglou、S、Vanin、EF、et al.(2004).Correction of multi-gene deficiency in vivo using a single ’self-cleaving’ 2A peptide-based retroviral vector.Nat Biotechnol 22:589-94.
12. Yam、P、Jensen、M、Akkina、R、Anderson、J、Villacres、MC、Wu、J et al.(2006). Ex vivo selection and expansion of cells based on expression of a mutated inosine monophosphate dehydrogenase 2 after HIV vector transduction:effects on lymphocytes、 monocytes、and CD34+stem cells.Mol Ther 14:236-44.
13. Pelloquin、F、Lamelin、JP、and Lenoir、GM(1986).Human B lymphocytes immortalization by Epstein-Barr virus in the presence of cyclosporin A.In Vitro Cell Dev Biol 22:689-94.
Claims (13)
- EGFRドメインIII、EGFRドメインIV及びEGFR膜貫通ドメインを含むが、EGFRドメインI、EGFRドメインII、EGFR膜近傍ドメイン、及びEGFRチロシンキナーゼドメインからなるドメインの全てを欠失した、改変上皮増殖因子レセプタ(EGFR)をコードする核酸分子を含むヒトT細胞を濃縮又は選択するインビトロでの方法であって、ここで、前記EGFRには、(i)内因性シグナル伝達機能又は輸送機能はなく;(ii)治療用抗EGFR抗体に結合し;(iii)内因性EGFRリガンドに結合せず;かつ、(iv)マーカーとして作用し、かつ、ここで、前記方法は、前記核酸分子を含むヒトT細胞を含む細胞の集団を、前記EGFRに結合する抗EGFR抗体と接触させるステップを含む、方法。
- 核酸分子は、配列番号2の第67~1071番目のヌクレオチドを含む、請求項1に記載のインビトロでの方法。
- 核酸分子は、配列番号3の第23~357番目の残基を含むアミノ酸配列をコードする、請求項1に記載のインビトロでの方法。
- 核酸分子は、さらに、GMCSFRアルファ鎖シグナル配列を含む、請求項1に記載のインビトロでの方法。
- 核酸分子は、配列番号2を含む、請求項4に記載のインビトロでの方法。
- 核酸分子は、配列番号3と少なくとも90%の同一性があるアミノ酸配列をコードする、請求項4に記載のインビトロでの方法。
- 核酸分子は、配列番号3を含むアミノ酸配列をコードする、請求項4に記載のインビトロでの方法。
- 核酸分子は、ベクター内へ挿入される、請求項1に記載のインビトロでの方法。
- 核酸分子は、腫瘍関連抗原に特異的なキメラ抗原レセプタにC末端2A開裂性リンカを介して結合した改変EGFRを含むコンストラクトの一部であり、前記腫瘍関連抗原は、CD19、CD20、及びCD22からなる群から選択される、請求項1に記載のインビトロでの方法。
- 改変EGFRは、コドン最適化抗CD19共刺激キメラ抗原レセプタ(CD 19CAR)及びC末端2A開裂性リンカに結合する、請求項1に記載のインビトロでの方法。
- CD 19CAR及びC末端2A開裂性リンカに結合した改変上皮増殖因子レセプタ(EGFR)をコードする核酸分子を含むヒトT細胞を濃縮又は選択するインビトロでの方法であって、前記核酸分子は、配列番号6を含むアミノ酸配列をコードする、インビトロでの方法。
- 核酸分子は、ヒトT細胞の集団にベクター内に挿入されて形質導入される、請求項11に記載のインビトロでの方法。
- 改変上皮増殖因子レセプタ(EGFR)をコードする核酸分子を含むヒトT細胞を含む細胞の集団を以前に投与された患者に、抗EGFR抗体を投与して、改変EGFRをコードする核酸分子を含むヒトT細胞を枯渇させることにより、前記患者を治療するための、抗EGFR抗体を含む医薬組成物であって、
ここで、前記抗EGFR抗体は、前記改変EGFRに結合し;
ここで、前記改変EGFRは、EGFRドメインIII、EGFRドメインIV及びEGFR膜貫通ドメインを含むが、EGFRドメインI、EGFRドメインII、EGFR膜近傍ドメイン、及びEGFRチロシンキナーゼドメインからなるドメインの全てを欠失し、かつ、(i)内因性シグナル伝達機能又は輸送機能はなく;(ii)治療用抗EGFR抗体に結合し;(iii)内因性EGFRリガンドには結合せず;かつ、(iv)マーカーとして作用する、
医薬組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022120718A JP7320656B2 (ja) | 2009-11-03 | 2022-07-28 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25756709P | 2009-11-03 | 2009-11-03 | |
US61/257,567 | 2009-11-03 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019046818A Division JP6753975B2 (ja) | 2009-11-03 | 2019-03-14 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022120718A Division JP7320656B2 (ja) | 2009-11-03 | 2022-07-28 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2021006035A JP2021006035A (ja) | 2021-01-21 |
JP7116126B2 JP7116126B2 (ja) | 2022-08-09 |
JP7116126B6 true JP7116126B6 (ja) | 2022-08-22 |
Family
ID=43970727
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012537974A Active JP5956342B2 (ja) | 2009-11-03 | 2010-11-03 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2016120180A Active JP6267278B2 (ja) | 2009-11-03 | 2016-06-16 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2017165623A Active JP6499245B2 (ja) | 2009-11-03 | 2017-08-30 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2019046818A Active JP6753975B2 (ja) | 2009-11-03 | 2019-03-14 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2020139041A Active JP7116126B6 (ja) | 2009-11-03 | 2020-08-20 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2022120718A Active JP7320656B2 (ja) | 2009-11-03 | 2022-07-28 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012537974A Active JP5956342B2 (ja) | 2009-11-03 | 2010-11-03 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2016120180A Active JP6267278B2 (ja) | 2009-11-03 | 2016-06-16 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2017165623A Active JP6499245B2 (ja) | 2009-11-03 | 2017-08-30 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
JP2019046818A Active JP6753975B2 (ja) | 2009-11-03 | 2019-03-14 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022120718A Active JP7320656B2 (ja) | 2009-11-03 | 2022-07-28 | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) |
Country Status (14)
Country | Link |
---|---|
US (5) | US8802374B2 (ja) |
EP (3) | EP3527585B1 (ja) |
JP (6) | JP5956342B2 (ja) |
AU (4) | AU2010315243B2 (ja) |
CA (1) | CA2779526C (ja) |
DK (1) | DK2496698T3 (ja) |
ES (2) | ES2717629T3 (ja) |
HR (1) | HRP20190556T1 (ja) |
HU (1) | HUE044461T2 (ja) |
PL (1) | PL2496698T3 (ja) |
PT (1) | PT2496698T (ja) |
SI (1) | SI2496698T1 (ja) |
TR (1) | TR201904484T4 (ja) |
WO (1) | WO2011056894A2 (ja) |
Families Citing this family (281)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007054550A1 (en) | 2005-11-11 | 2007-05-18 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
WO2011003853A2 (en) | 2009-07-06 | 2011-01-13 | Boehringer Ingelheim International Gmbh | Process for drying of bibw2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
AU2010315243B2 (en) | 2009-11-03 | 2016-08-25 | City Of Hope | Truncated epidermal growth factor receptor (EGFRt) for transduced T cell selection |
US8828391B2 (en) * | 2011-05-17 | 2014-09-09 | Boehringer Ingelheim International Gmbh | Method for EGFR directed combination treatment of non-small cell lung cancer |
AU2013221672B2 (en) * | 2012-02-13 | 2017-11-09 | Seattle Children's Hospital D/B/A Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
BR112014020499A2 (pt) | 2012-02-22 | 2019-09-24 | Univ Pennsylvania | sequência de ácido nucleico isolada, célula - t, vetor, e, população persistente de células - t |
IN2014DN07441A (ja) * | 2012-02-23 | 2015-04-24 | Smith & Nephew Inc | |
SI2884999T1 (sl) * | 2012-08-20 | 2021-05-31 | Fred Hutchinson Cancer Research Center | Metoda in sestavki za celično imunoterapijo |
US9657105B2 (en) * | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
KR102339240B1 (ko) | 2013-10-15 | 2021-12-15 | 더 스크립스 리서치 인스티튜트 | 펩타이드 키메라 항원 수용체 t 세포 스위치 및 이의 용도 |
EP3071686B1 (en) | 2013-11-22 | 2020-07-22 | Cellectis SA | Method for generating batches of allogeneic t-cells with averaged potency |
US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
CN107074957B (zh) * | 2014-01-13 | 2021-05-07 | 希望之城公司 | 在Fc间隔物区中具有突变的嵌合抗原受体(CAR)及其使用方法 |
MX370788B (es) * | 2014-04-03 | 2020-01-06 | Cellectis | Receptores de antígeno quimérico específico de cd33 para inmunoterapia de cáncer. |
CA2940671A1 (en) * | 2014-04-07 | 2015-10-15 | Novartis Ag | Treatment of cancer using anti-cd19 chimeric antigen receptor |
MY192522A (en) * | 2014-04-10 | 2022-08-25 | Seattle Childrens Hospital Dba Seattle Childrens Res Inst | Defined composition gene modified t-cell products |
EP3134095B1 (en) | 2014-04-25 | 2020-04-22 | Bluebird Bio, Inc. | Improved methods for manufacturing adoptive cell therapies |
WO2015188119A1 (en) | 2014-06-06 | 2015-12-10 | Bluebird Bio, Inc. | Improved t cell compositions |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
SG11201700476VA (en) | 2014-07-21 | 2017-02-27 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
SG10201913765YA (en) | 2014-07-21 | 2020-03-30 | Novartis Ag | Treatment of cancer using a cd33 chimeric antigen receptor |
AU2015292590B2 (en) | 2014-07-24 | 2020-01-16 | 2Seventy Bio, Inc. | BCMA chimeric antigen receptors |
EP4205749A1 (en) | 2014-07-31 | 2023-07-05 | Novartis AG | Subset-optimized chimeric antigen receptor-containing cells |
WO2016025880A1 (en) | 2014-08-14 | 2016-02-18 | Novartis Ag | Treatment of cancer using gfr alpha-4 chimeric antigen receptor |
DK3183268T3 (da) | 2014-08-19 | 2020-05-11 | Univ Pennsylvania | Behandling af cancer ved anvendelse af en cd123-kimær antigenreceptor |
CN114621969A (zh) | 2014-09-17 | 2022-06-14 | 诺华股份有限公司 | 用于过继免疫疗法的具有嵌合受体的靶向细胞毒性细胞 |
SG11201702895SA (en) | 2014-10-08 | 2017-05-30 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
RS60685B1 (sr) | 2014-11-05 | 2020-09-30 | Juno Therapeutics Inc | Postupci za transdukciju i obradu ćelija |
US20180334490A1 (en) | 2014-12-03 | 2018-11-22 | Qilong H. Wu | Methods for b cell preconditioning in car therapy |
MX2017007138A (es) | 2014-12-03 | 2017-08-28 | Juno Therapeutics Inc | Metodos y composiciones para terapia celular adoptiva. |
AU2015357533B2 (en) | 2014-12-05 | 2021-10-07 | Eureka Therapeutics, Inc. | Antibodies targeting B-cell maturation antigen and methods of use |
WO2016090337A1 (en) | 2014-12-05 | 2016-06-09 | Memorial Sloan-Kettering Cancer Center | Chimeric antigen receptors targeting fc receptor-like 5 and uses thereof |
IL252617B (en) | 2014-12-05 | 2022-09-01 | Memorial Sloan Kettering Cancer Center | All B-cell maturation antigen-directed chimeric antigen receptors and their uses |
NZ733025A (en) | 2014-12-12 | 2022-01-28 | 2Seventy Bio Inc | Bcma chimeric antigen receptors |
SG11201705293WA (en) | 2014-12-29 | 2017-07-28 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
MA41346A (fr) | 2015-01-12 | 2017-11-21 | Juno Therapeutics Inc | Eléments régulateurs post-transcriptionnels d'hépatite modifiée |
US11161907B2 (en) | 2015-02-02 | 2021-11-02 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
US10800828B2 (en) | 2015-03-26 | 2020-10-13 | The Scripps Research Institute | Switchable non-scFv chimeric receptors, switches, and methods of use thereof to treat cancer |
ES2876974T3 (es) | 2015-04-07 | 2021-11-15 | Novartis Ag | Combinación de terapia con receptor de antígeno quimérico y derivados de amino pirimidina |
MX2017012939A (es) | 2015-04-08 | 2018-05-22 | Novartis Ag | Terapias cd20, terapias cd22 y terapias de combinacion con una celula que expresa un receptor quimerico de antigeno (car) de cd19. |
GB201506223D0 (en) * | 2015-04-13 | 2015-05-27 | Ucl Business Plc | Chimeric protein |
US11091546B2 (en) | 2015-04-15 | 2021-08-17 | The Scripps Research Institute | Optimized PNE-based chimeric receptor T cell switches and uses thereof |
AU2016249005B2 (en) | 2015-04-17 | 2022-06-16 | Novartis Ag | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
JP6570109B2 (ja) * | 2015-05-15 | 2019-09-04 | 国立大学法人名古屋大学 | キメラ抗原レセプター遺伝子発現システム |
PT3294764T (pt) | 2015-05-15 | 2021-02-15 | Hope City | Composições de recetores de antigénios quiméricos |
EP3303381A1 (en) | 2015-05-29 | 2018-04-11 | Fred Hutchinson Cancer Research Center | Compositions for cellular immunotherapy |
JP6949728B2 (ja) | 2015-05-29 | 2021-10-13 | ジュノー セラピューティクス インコーポレイテッド | 遺伝子操作された細胞における阻害相互作用を調節するための組成物および方法 |
EP3325504A1 (en) | 2015-07-21 | 2018-05-30 | Novartis AG | Methods for improving the efficacy and expansion of immune cells |
CN108174604B (zh) | 2015-08-07 | 2023-06-23 | 西雅图儿童医院(Dba西雅图儿童研究所) | 用于实体瘤靶向的双特异性car t细胞 |
CN108780084B (zh) | 2015-09-03 | 2022-07-22 | 诺华股份有限公司 | 预测细胞因子释放综合征的生物标志物 |
CA2997551A1 (en) | 2015-09-04 | 2017-03-09 | Memorial Sloan Kettering Cancer Center | Immune cell compositions and methods of use |
MX2018005674A (es) | 2015-11-04 | 2019-01-10 | J Priceman Saul | Receptores de antigenos quimericos dirigidos a her2. |
WO2017079570A2 (en) * | 2015-11-04 | 2017-05-11 | Duke University | Splise-switching oligonucleotides and methods of use |
MA44314A (fr) | 2015-11-05 | 2018-09-12 | Juno Therapeutics Inc | Récepteurs chimériques contenant des domaines induisant traf, et compositions et méthodes associées |
US20200297760A1 (en) | 2015-12-03 | 2020-09-24 | Juno Therapeutics, Inc. | Compositions and methods for reducing immune responses against chimeric antigen receptors |
CA3007262A1 (en) | 2015-12-03 | 2017-06-08 | Lucas James Thompson | Modified chimeric receptors and related compositions and methods |
ES2901795T3 (es) | 2015-12-04 | 2022-03-23 | Juno Therapeutics Inc | Métodos y composiciones relacionadas con la toxicidad asociada con la terapia celular |
IL259747B (en) | 2015-12-04 | 2022-09-01 | Memorial Sloan Kettering Cancer Center | Antibodies against fcrl5 and methods of their use |
WO2017099712A1 (en) | 2015-12-07 | 2017-06-15 | Bluebird Bio, Inc. | Improved t cell compositions |
AU2016366226B2 (en) | 2015-12-09 | 2023-06-01 | Memorial Sloan Kettering Cancer Center | Immune cell compositions and methods of using same |
JP2019500874A (ja) | 2015-12-28 | 2019-01-17 | ノバルティス アーゲー | キメラ抗原受容体発現細胞の作製方法 |
US10919950B2 (en) * | 2016-01-14 | 2021-02-16 | Seattle Children's Hospital | Tumor-specific IFNA secretion by car T-cells to reprogram the solid tumor microenvironment |
AU2017225733A1 (en) | 2016-03-04 | 2018-09-27 | Novartis Ag | Cells expressing multiple chimeric antigen receptor (CAR) molecules and uses therefore |
WO2017161208A1 (en) | 2016-03-16 | 2017-09-21 | Juno Therapeutics, Inc. | Methods for determining dosing of a therapeutic agent and related treatments |
MA43759A (fr) | 2016-03-16 | 2018-11-28 | Jason Connor | Procédés de conception adaptative d'un régime de traitement et traitements associés |
EP3430038B1 (en) | 2016-03-18 | 2021-06-16 | Fred Hutchinson Cancer Research Center | Compositions and methods for cd20 immunotherapy |
WO2020047527A2 (en) | 2018-09-02 | 2020-03-05 | F1 Bioventures, Llc | Methods and compositions for genetically modifying lymphocytes in blood or in enriched pbmcs |
MX2018011345A (es) | 2016-03-19 | 2019-05-27 | F1 Oncology Inc | Métodos y composiciones para transducir linfocitos y expansión regulada de los mismos. |
WO2017165571A1 (en) | 2016-03-22 | 2017-09-28 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Early intervention methods to prevent or ameliorate toxicity |
CN109415409B (zh) | 2016-04-01 | 2022-03-15 | 亘喜生物科技(上海)有限公司 | Flag标记的cd19-car-t细胞 |
US11377637B2 (en) | 2016-04-15 | 2022-07-05 | Memorial Sloan Kettering Cancer Center | Transgenic T cell and chimeric antigen receptor T cell compositions and related methods |
CN105820250B (zh) * | 2016-04-29 | 2019-04-30 | 中国人民解放军第四军医大学 | 一种抗basigin人源化抗体及其应用 |
CN116850305A (zh) | 2016-05-06 | 2023-10-10 | 朱诺治疗学股份有限公司 | 基因工程化细胞及其制备方法 |
US20210177896A1 (en) | 2016-06-02 | 2021-06-17 | Novartis Ag | Therapeutic regimens for chimeric antigen receptor (car)- expressing cells |
JP2019517518A (ja) | 2016-06-03 | 2019-06-24 | メモリアル スローン ケタリング キャンサー センター | 早期治療選択肢としての養子細胞療法 |
MA45341A (fr) | 2016-06-06 | 2019-04-10 | Hutchinson Fred Cancer Res | Procédés de traitement de malignités de lymphocytes b au moyen d'une thérapie cellulaire adoptive |
US11787848B2 (en) | 2016-06-08 | 2023-10-17 | Precigen, Inc. | CD33 specific chimeric antigen receptors |
MX2018015414A (es) * | 2016-06-30 | 2019-08-01 | Hoffmann La Roche | Terapia de célula t adoptiva mejorada. |
EP3472318B1 (en) | 2016-07-08 | 2023-09-06 | Exuma Biotech Corp. | Methods and compositions for transducing lymphocytes and regulating the activity thereof |
JP7219376B2 (ja) | 2016-07-15 | 2023-02-08 | ノバルティス アーゲー | キメラ抗原受容体をキナーゼ阻害薬と併用して使用したサイトカイン放出症候群の治療及び予防 |
AU2017301887A1 (en) | 2016-07-29 | 2019-02-07 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies against anti-CD19 antibodies |
KR20190036551A (ko) | 2016-08-01 | 2019-04-04 | 노파르티스 아게 | Pro-m2 대식세포 분자의 억제제를 병용하는, 키메라 항원 수용체를 이용한 암의 치료 |
CN109863242A (zh) | 2016-08-30 | 2019-06-07 | 纪念斯隆-凯特林癌症中心 | 用于治疗病毒感染和其它感染的免疫细胞组合物和使用方法 |
CN110139873A (zh) | 2016-10-03 | 2019-08-16 | 朱诺治疗学股份有限公司 | Hpv特异性结合分子 |
EP4190335A1 (en) | 2016-10-13 | 2023-06-07 | Juno Therapeutics, Inc. | Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators |
JP7149935B2 (ja) | 2016-10-19 | 2022-10-07 | ザ スクリプス リサーチ インスティテュート | ヒト化された標的化部分および/または最適化されたキメラ抗原受容体相互作用ドメインを有する、キメラ抗原受容体エフェクター細胞スイッチ、ならびにその使用 |
MA46783A (fr) | 2016-11-03 | 2019-09-11 | Juno Therapeutics Inc | Polythérapie de type thérapie cellulaire t et inhibiteur de btk |
CA3040914A1 (en) | 2016-11-03 | 2018-05-24 | Juno Therapeutics, Inc. | Combination therapy of a cell based therapy and a microglia inhibitor |
US11793833B2 (en) | 2016-12-02 | 2023-10-24 | Juno Therapeutics, Inc. | Engineered B cells and related compositions and methods |
WO2018102787A1 (en) | 2016-12-03 | 2018-06-07 | Juno Therapeutics, Inc. | Methods for determining car-t cells dosing |
BR112019011025A2 (pt) | 2016-12-03 | 2019-10-08 | Juno Therapeutics Inc | métodos para modulação de células t car |
MX2019006288A (es) | 2016-12-03 | 2020-10-01 | Juno Therapeutics Inc | Metodos y composiciones para el uso de celulas t terapeuticas en combinacion con inhibidores de quinasa. |
MA46998A (fr) | 2016-12-05 | 2019-10-09 | Juno Therapeutics Inc | Production de cellules modifiées pour une thérapie cellulaire adoptive |
CA3045665A1 (en) | 2016-12-12 | 2018-06-21 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Chimeric transcription factor variants with augmented sensitivity to drug ligand induction of transgene expression in mammalian cells |
WO2018132518A1 (en) | 2017-01-10 | 2018-07-19 | Juno Therapeutics, Inc. | Epigenetic analysis of cell therapy and related methods |
EP3571294A1 (en) | 2017-01-18 | 2019-11-27 | F1 Oncology, Inc. | Methods of transducing and expanding immune cells and uses thereof |
KR20190130559A (ko) | 2017-01-18 | 2019-11-22 | 에프1 온콜로지, 인코포레이티드 | Axl 또는 ror2에 대한 키메라 항원 수용체 및 이의 사용 방법 |
MA47325A (fr) | 2017-01-20 | 2019-11-27 | Juno Therapeutics Gmbh | Conjugués de surface cellulaire et compositions cellulaires et méthodes associées |
US11649288B2 (en) | 2017-02-07 | 2023-05-16 | Seattle Children's Hospital | Phospholipid ether (PLE) CAR T cell tumor targeting (CTCT) agents |
MX2019009552A (es) | 2017-02-17 | 2019-10-02 | Hutchinson Fred Cancer Res | Terapias de combinacion para el tratamiento de canceres relacionados con el antigeno de maduracion de celulas b (bcma) y trastornos autoinmunitarios. |
MX2019010171A (es) | 2017-02-27 | 2019-10-15 | Juno Therapeutics Inc | Composiciones, articulos de fabricacion y metodos relacionados con la dosificacion en la terapia celular. |
JP7178355B2 (ja) | 2017-02-28 | 2022-11-25 | エンドサイト・インコーポレイテッド | Car t細胞療法のための組成物および方法 |
SG11201907814SA (en) | 2017-03-03 | 2019-09-27 | F1 Oncology Inc | Methods and compositions for transducing and expanding lymphocytes and regulating the activity thereof |
AU2018231190B2 (en) | 2017-03-08 | 2023-05-25 | Memorial Sloan Kettering Cancer Center | Immune cell compositions and methods of use |
CN110913690A (zh) | 2017-03-14 | 2020-03-24 | 朱诺治疗学股份有限公司 | 用于低温储存的方法 |
CA3056261A1 (en) * | 2017-04-07 | 2018-10-11 | Juno Therapeutics, Inc. | Engineered cells expressing prostate-specific membrane antigen (psma) or a modified form thereof and related methods |
JP7355650B2 (ja) | 2017-04-14 | 2023-10-03 | ジュノー セラピューティクス インコーポレイテッド | 細胞表面グリコシル化を評価するための方法 |
KR20240059648A (ko) | 2017-04-19 | 2024-05-07 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 조작된 항원 수용체를 발현하는 면역 세포 |
US20200055948A1 (en) | 2017-04-28 | 2020-02-20 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
PT3618842T (pt) | 2017-05-01 | 2024-01-12 | Juno Therapeutics Inc | Combinação de uma terapia celular e de um composto imunomodulador |
CN110891567B (zh) | 2017-05-24 | 2024-01-09 | 效应治疗股份有限公司 | 用于改善的抗肿瘤免疫应答的组合物和方法 |
US11413310B2 (en) | 2017-06-02 | 2022-08-16 | Juno Therapeutics, Inc. | Articles of manufacture and methods for treatment using adoptive cell therapy |
EP3631468A1 (en) | 2017-06-02 | 2020-04-08 | Juno Therapeutics, Inc. | Articles of manufacture and methods related to toxicity associated with cell therapy |
IL306102A (en) * | 2017-06-07 | 2023-11-01 | Precigen Inc | Expression of new cell markers |
MX2019015155A (es) | 2017-06-29 | 2020-08-03 | Juno Therapeutics Inc | Modelo de raton para valorar toxicidades asociadas con inmunoterapias. |
CA3070998A1 (en) * | 2017-07-25 | 2019-01-31 | Board Of Regents, The University Of Texas System | Enhanced chimeric antigen receptors and use thereof |
CN107603995A (zh) * | 2017-07-31 | 2018-01-19 | 北京普瑞金科技有限公司 | 一种cd19 cart及其应用 |
EP3441471A1 (en) * | 2017-08-08 | 2019-02-13 | CEVEC Pharmaceuticals GmbH | Use of constitutively active variants of growth factor receptors as selection makers for the generation of stable producer cell lines |
BR112020001605A2 (pt) | 2017-08-09 | 2020-08-11 | Juno Therapeutics Inc | métodos para produzir composições de células geneticamente modificadas e composições relacionadas |
EP3664835A1 (en) | 2017-08-09 | 2020-06-17 | Juno Therapeutics, Inc. | Methods and compositions for preparing genetically engineered cells |
MA50057A (fr) | 2017-09-01 | 2020-07-08 | Juno Therapeutics Inc | Expression génique et évaluation d'un risque de développement d'une toxicité suite à une thérapie cellulaire |
EP3679370A1 (en) | 2017-09-07 | 2020-07-15 | Juno Therapeutics, Inc. | Methods of identifying cellular attributes related to outcomes associated with cell therapy |
CN111148533A (zh) | 2017-09-19 | 2020-05-12 | 麻省理工学院 | 用于嵌合抗原受体t细胞疗法的组合物及其用途 |
CN109517820B (zh) | 2017-09-20 | 2021-09-24 | 北京宇繁生物科技有限公司 | 一种靶向HPK1的gRNA以及HPK1基因编辑方法 |
WO2019070856A1 (en) | 2017-10-03 | 2019-04-11 | Precision Biosciences, Inc. | MODIFIED EPIDERMAL GROWTH FACTOR RECEPTOR PEPTIDES FOR USE IN GENETICALLY MODIFIED CELLS |
KR20200104284A (ko) | 2017-10-03 | 2020-09-03 | 주노 쎄러퓨티크스 인코퍼레이티드 | Hpv-특이적 결합 분자 |
US20200370012A1 (en) | 2017-10-25 | 2020-11-26 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
MA49911A (fr) | 2017-11-01 | 2020-06-24 | Juno Therapeutics Inc | Anticorps et récepteurs antigéniques chimériques spécifiques de l'antigene de maturation des lymphocytes b |
MA50855A (fr) | 2017-11-01 | 2020-09-09 | Juno Therapeutics Inc | Procédé de génération de compositions thérapeutiques de cellules modifiées |
MA50860A (fr) | 2017-11-01 | 2020-09-09 | Juno Therapeutics Inc | Récepterus chimériques d'antigène contre l'antigène de maturation des cellules b et polynucleotides codants |
WO2019089982A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Method of assessing activity of recombinant antigen receptors |
US11564946B2 (en) | 2017-11-01 | 2023-01-31 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
MX2020004239A (es) | 2017-11-01 | 2020-09-09 | Juno Therapeutics Inc | Proceso para producir una composicion de celulas t. |
WO2019089858A2 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
AU2018362014A1 (en) | 2017-11-03 | 2020-05-28 | Sorrento Therapeutics, Inc. | CD38-directed chimeric antigen receptor constructs |
MX2020004568A (es) | 2017-11-06 | 2020-10-05 | Juno Therapeutics Inc | Combinación de una terapia celular y un inhibidor de gamma secretasa. |
EP3707160A1 (en) | 2017-11-10 | 2020-09-16 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Chimeric antigen receptors targeting tumor antigens |
MA51210A (fr) | 2017-12-01 | 2020-10-07 | Juno Therapeutics Inc | Procédés de dosage et de modulation de cellules génétiquement modifiées |
US20200384025A1 (en) | 2017-12-08 | 2020-12-10 | Juno Therapeutics, Inc. | Process for producing a composition of engineered t cells |
AU2018379094A1 (en) | 2017-12-08 | 2020-06-25 | Juno Therapeutics, Inc. | Phenotypic markers for cell therapy and related methods |
EP3720949A1 (en) | 2017-12-08 | 2020-10-14 | Juno Therapeutics, Inc. | Serum-free media formulation for culturing cells and methods of use thereof |
US12006356B2 (en) | 2017-12-15 | 2024-06-11 | Juno Therapeutics, Inc. | Anti-CCT5 binding molecules and chimeric antigen receptors comprising the same |
CN109971723B (zh) * | 2017-12-28 | 2023-07-07 | 上海细胞治疗研究院 | 包含CD40抗体与muc1特异性嵌合抗原受体基因的T细胞及其用途 |
TW201940182A (zh) | 2018-01-22 | 2019-10-16 | 美商安德賽特公司 | Car t 細胞之使用方法 |
US20210069246A1 (en) | 2018-01-31 | 2021-03-11 | Celgene Corporation | Combination therapy using adoptive cell therapy and checkpoint inhibitor |
TWI728309B (zh) | 2018-02-01 | 2021-05-21 | 大陸商南京馴鹿醫療技術有限公司 | 一種結合bcma的嵌合抗原受體(car)及其應用 |
JP6968389B2 (ja) | 2018-02-01 | 2021-11-17 | 南京馴鹿医療技術有限公司 | Bcmaに結合するキメラ抗原受容体(car)及びその応用 |
US20210046159A1 (en) | 2018-03-09 | 2021-02-18 | Ospedale San Raffaele S.R.L. | Il-1 antagonist and toxicity induced by cell therapy |
EA202091984A1 (ru) * | 2018-03-14 | 2021-02-18 | Сиэтл Чилдрен'С Хоспитал (Дба Сиэтл Чилдрен'С Ресёрч Инститьют) | Направленная дзетакинами т-клеточная иммунотерапия, нацеленная на рецептор il-13 альфа 2 |
RU2020136054A (ru) | 2018-04-05 | 2022-05-06 | Джуно Терапьютикс, Инк. | Т-клетки, экспрессирующие рекомбинантный рецептор, соответствующие полинуклеотиды и способы |
CN112566698A (zh) | 2018-04-05 | 2021-03-26 | 朱诺治疗学股份有限公司 | T细胞受体和表达该t细胞受体的工程化细胞 |
BR112020020245A2 (pt) | 2018-04-05 | 2021-04-06 | Editas Medicine, Inc. | Métodos de produzir células expressando um receptor recombinante e composições relacionadas |
WO2019213282A1 (en) | 2018-05-01 | 2019-11-07 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
CN112584902A (zh) | 2018-05-03 | 2021-03-30 | 朱诺治疗学股份有限公司 | 嵌合抗原受体(car)t细胞疗法和激酶抑制剂的组合疗法 |
CN110526983B (zh) * | 2018-05-24 | 2022-02-11 | 北京马力喏生物科技有限公司 | 改良型抗cd19 car-t细胞 |
WO2019227003A1 (en) | 2018-05-25 | 2019-11-28 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
CA3101641A1 (en) * | 2018-06-04 | 2019-12-12 | Intrexon Corporation | Muc16 specific chimeric antigen receptors and uses thereof |
WO2019237035A1 (en) | 2018-06-08 | 2019-12-12 | Intellia Therapeutics, Inc. | Compositions and methods for immunooncology |
SG11202011830SA (en) | 2018-06-13 | 2020-12-30 | Novartis Ag | Bcma chimeric antigen receptors and uses thereof |
CA3106544A1 (en) | 2018-08-08 | 2020-02-13 | Mitchell Ho | High affinity monoclonal antibodies targeting glypican-2 and uses thereof |
EP3833759A1 (en) | 2018-08-09 | 2021-06-16 | Juno Therapeutics, Inc. | Methods for assessing integrated nucleic acids |
US20210163893A1 (en) | 2018-08-09 | 2021-06-03 | Juno Therapeutics, Inc. | Processes for generating engineered cells and compositions thereof |
US20210221903A1 (en) * | 2018-08-14 | 2021-07-22 | Hrain Biotechnology Co., Ltd. | Bcma-targeting chimeric antigen receptor and uses thereof |
EP3844265A2 (en) | 2018-08-31 | 2021-07-07 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
US20220364055A1 (en) | 2018-08-31 | 2022-11-17 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
CN113167796A (zh) | 2018-09-11 | 2021-07-23 | 朱诺治疗学股份有限公司 | 对工程化细胞组合物进行质谱分析的方法 |
US20220047633A1 (en) | 2018-09-28 | 2022-02-17 | Novartis Ag | Cd22 chimeric antigen receptor (car) therapies |
JP2022502037A (ja) | 2018-09-28 | 2022-01-11 | マサチューセッツ インスティテュート オブ テクノロジー | コラーゲンに局在化される免疫調節分子およびその方法 |
US20210347851A1 (en) | 2018-09-28 | 2021-11-11 | Novartis Ag | Cd19 chimeric antigen receptor (car) and cd22 car combination therapies |
US20220002669A1 (en) | 2018-10-31 | 2022-01-06 | Juno Therapeutics Gmbh | Methods for selection and stimulation of cells and apparatus for same |
KR20210113169A (ko) | 2018-11-01 | 2021-09-15 | 주노 쎄러퓨티크스 인코퍼레이티드 | Β세포 성숙 항원에 특이적인 키메라 항원 수용체를 이용한 치료 방법 |
MX2021005022A (es) | 2018-11-01 | 2021-09-08 | Juno Therapeutics Inc | Receptores de antigenos quimericos especificos para el miembro d del grupo 5 de la clase c del receptor acoplado a proteina g (gprc5d). |
ES2968737T3 (es) | 2018-11-06 | 2024-05-13 | Juno Therapeutics Inc | Proceso para producir células T manipuladas genéticamente |
CA3117978A1 (en) | 2018-11-08 | 2020-05-14 | Juno Therapeutics, Inc. | Methods and combinations for treatment and t cell modulation |
BR112021009420A2 (pt) | 2018-11-16 | 2021-11-23 | Juno Therapeutics Inc | Métodos de dosagem de células t manipuladas para o tratamento de malignidades de células b |
US20220088070A1 (en) | 2018-11-30 | 2022-03-24 | Juno Therapeutics, Inc. | Methods for treatment using adoptive cell therapy |
EP3886894B1 (en) | 2018-11-30 | 2024-03-13 | Juno Therapeutics, Inc. | Methods for dosing and treatment of b cell malignancies in adoptive cell therapy |
US20220064324A1 (en) | 2019-01-08 | 2022-03-03 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Cross species single domain antibodies targeting mesothelin for treating solid tumors |
CN113784987A (zh) | 2019-01-22 | 2021-12-10 | 美国政府(由卫生和人类服务部的部长所代表) | 靶向磷脂酰肌醇蛋白聚糖-1的高亲和力单克隆抗体和使用方法 |
EP3917570A1 (en) | 2019-01-29 | 2021-12-08 | Juno Therapeutics, Inc. | Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1) |
EP3773918A4 (en) | 2019-03-05 | 2022-01-05 | Nkarta, Inc. | CD19 DIRECTED CHIMERIC ANTIGEN RECEPTORS AND THEIR USES IN IMMUNOTHERAPY |
AU2020243787B9 (en) * | 2019-03-15 | 2023-09-28 | Asclepius (Suzhou) Technology Company Group Co., Ltd. | ROBO1 CAR-NK cell carrying suicide gene, preparation method therefor and application thereof |
US20220168389A1 (en) | 2019-04-12 | 2022-06-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
CA3136742A1 (en) | 2019-05-01 | 2020-11-05 | Juno Therapeutics, Inc. | Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods |
MX2021013219A (es) | 2019-05-01 | 2022-02-17 | Juno Therapeutics Inc | Celulas que expresan un receptor recombinante de un locus de tgfbr2 modificado, polinucleotidos relacionados y metodos. |
JP2022535380A (ja) | 2019-06-07 | 2022-08-08 | ジュノー セラピューティクス インコーポレイテッド | 自動化t細胞培養 |
KR20220034782A (ko) | 2019-06-12 | 2022-03-18 | 주노 쎄러퓨티크스 인코퍼레이티드 | 세포 매개 세포 독성 요법 및 친생존 bcl2 패밀리 단백질 억제제의 병용 요법 |
EP3990491A1 (en) | 2019-06-26 | 2022-05-04 | Massachusetts Institute of Technology | Immunomodulatory fusion protein-metal hydroxide complexes and methods thereof |
CN112195154B (zh) * | 2019-07-08 | 2024-03-29 | 江苏汇智生物科技有限公司 | 一种基因改造表达改造型pla2r受体的细胞及其应用 |
EP3769816A1 (en) * | 2019-07-25 | 2021-01-27 | Ospedale Pediatrico Bambino Gesù | Car-cd123 vector and uses thereof |
EP4004216A1 (en) | 2019-07-25 | 2022-06-01 | Precision BioSciences, Inc. | Compositions and methods for sequential stacking of nucleic acid sequences into a genomic locus |
JP2022544825A (ja) | 2019-08-20 | 2022-10-21 | プレシジョン バイオサイエンシズ,インク. | 細胞免疫療法のためのリンパ球枯渇投与レジメン |
US20220298222A1 (en) | 2019-08-22 | 2022-09-22 | Juno Therapeutics, Inc. | Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods |
US20220392613A1 (en) | 2019-08-30 | 2022-12-08 | Juno Therapeutics, Inc. | Machine learning methods for classifying cells |
CN114729041A (zh) | 2019-10-22 | 2022-07-08 | 美国政府(由卫生和人类服务部的部长所代表) | 用于治疗多种实体瘤的靶向b7h3(cd276)的高亲和力纳米抗体 |
JP2023500318A (ja) | 2019-10-30 | 2023-01-05 | ジュノ セラピューティクス ゲーエムベーハー | 細胞選択および/または細胞刺激デバイスならびに使用方法 |
JP2022554348A (ja) | 2019-11-05 | 2022-12-28 | ジュノー セラピューティクス インコーポレイテッド | 治療用t細胞組成物の属性を決定する方法 |
CN114980918A (zh) | 2019-11-07 | 2022-08-30 | 朱诺治疗学股份有限公司 | T细胞疗法与(s)-3-[4-(4-吗啉-4-基甲基-苄氧基)-1-氧代-1,3-二氢-异吲哚-2-基]-哌啶-2,6-二酮的组合 |
AR120566A1 (es) | 2019-11-26 | 2022-02-23 | Novartis Ag | Receptores de antígeno quiméricos y sus usos |
KR20220122656A (ko) | 2019-12-06 | 2022-09-02 | 주노 쎄러퓨티크스 인코퍼레이티드 | Gprc5d-표적화 결합 도메인에 대한 항-이디오타입 항체 및 관련 조성물 및 방법 |
WO2021113776A1 (en) | 2019-12-06 | 2021-06-10 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods |
MX2022006715A (es) | 2019-12-06 | 2022-09-23 | Juno Therapeutics Inc | Metodos relacionados con toxicidad y respuesta asociada con terapia celular para tratar neoplasias malignas de celulas b. |
KR20220145341A (ko) | 2020-01-24 | 2022-10-28 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법에서 여포성 림프종 및 변연부 림프종의 투여 및 치료 방법 |
US20230090117A1 (en) | 2020-01-28 | 2023-03-23 | Juno Therapeutics, Inc. | Methods for t cell transduction |
EP4103203A1 (en) | 2020-02-12 | 2022-12-21 | Juno Therapeutics, Inc. | Bcma-directed chimeric antigen receptor t cell compositions and methods and uses thereof |
CA3169672A1 (en) | 2020-02-12 | 2021-08-19 | Juno Therapeutics, Inc. | Cd19-directed chimeric antigen receptor t cell compositions and methods and uses thereof |
WO2021163618A1 (en) | 2020-02-14 | 2021-08-19 | Novartis Ag | Method of predicting response to chimeric antigen receptor therapy |
WO2021173674A1 (en) | 2020-02-26 | 2021-09-02 | A2 Biotherapeutics, Inc. | Polypeptides targeting mage-a3 peptide-mhc complexes and methods of use thereof |
CN115397460A (zh) | 2020-02-27 | 2022-11-25 | 诺华股份有限公司 | 制备表达嵌合抗原受体的细胞的方法 |
KR20220146530A (ko) | 2020-02-27 | 2022-11-01 | 노파르티스 아게 | 키메라 항원 수용체-발현 세포의 제조 방법 |
JP2023517063A (ja) | 2020-03-10 | 2023-04-21 | マサチューセッツ インスティテュート オブ テクノロジー | 操作されたメモリー様nk細胞を作製するための方法およびその組成物 |
CN115485295A (zh) | 2020-03-10 | 2022-12-16 | 麻省理工学院 | NPM1c阳性癌症的免疫疗法的组合物和方法 |
CA3159639A1 (en) * | 2020-03-20 | 2021-09-23 | Lyell Immunopharma, Inc. | Novel recombinant cell surface markers |
US20230149462A1 (en) | 2020-04-10 | 2023-05-18 | Juno Therapeutics, Inc. | Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen |
AU2021263765A1 (en) | 2020-04-28 | 2022-12-01 | Juno Therapeutics, Inc. | Combination of BCMA-directed T cell therapy and an immunomodulatory compound |
WO2021221782A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Chimeric antigen receptor-targeting ligands and uses thereof |
WO2021221783A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Methods for identifying chimeric antigen receptor-targeting ligands and uses thereof |
JP2023528215A (ja) | 2020-05-13 | 2023-07-04 | ジュノー セラピューティクス インコーポレイテッド | 臨床応答に関連する特徴量の特定方法およびその使用 |
EP4150057A2 (en) | 2020-05-13 | 2023-03-22 | Juno Therapeutics, Inc. | Process for producing donor-batched cells expressing a recombinant receptor |
US20240216508A1 (en) | 2020-06-26 | 2024-07-04 | Juno Therapeutics Gmbh | Engineered t cells conditionally expressing a recombinant receptor, related polynucleotides and methods |
WO2022029660A1 (en) | 2020-08-05 | 2022-02-10 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods |
EP4196504A1 (en) | 2020-08-13 | 2023-06-21 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Igg4 hinge-containing chimeric antigen receptors targeting glypican-1 (gpc1) for treating solid tumors |
US20230399412A1 (en) | 2020-10-12 | 2023-12-14 | Nanjing IASO Biotechnology Co., Ltd. | Antibody and chimeric antigen receptor (car) binding to cd70, and application thereof |
US20230391852A1 (en) | 2020-10-26 | 2023-12-07 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting sars coronavirus spike protein and uses thereof |
WO2022089644A1 (zh) | 2020-11-01 | 2022-05-05 | 南京驯鹿医疗技术有限公司 | 靶向cd5的全人源抗体、全人源嵌合抗原受体(car)及其应用 |
US20230398148A1 (en) | 2020-11-04 | 2023-12-14 | Juno Therapeutics, Inc. | Cells expressing a chimeric receptor from a modified invariant cd3 immunoglobulin superfamily chain locus and related polynucleotides and methods |
JP2023549504A (ja) | 2020-11-13 | 2023-11-27 | ノバルティス アーゲー | キメラ抗原受容体(car)発現細胞との組合せ療法 |
US20220195396A1 (en) * | 2020-12-03 | 2022-06-23 | Century Therapeutics, Inc. | Genetically Engineered Cells and Uses Thereof |
US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
TW202237638A (zh) | 2020-12-09 | 2022-10-01 | 日商武田藥品工業股份有限公司 | 烏苷酸環化酶c(gcc)抗原結合劑之組成物及其使用方法 |
JP2024502749A (ja) | 2020-12-16 | 2024-01-23 | ジュノー セラピューティクス インコーポレイテッド | フローサイトメトリー方法のための閾値ゲーティング |
WO2022133030A1 (en) | 2020-12-16 | 2022-06-23 | Juno Therapeutics, Inc. | Combination therapy of a cell therapy and a bcl2 inhibitor |
WO2022152185A1 (zh) | 2021-01-12 | 2022-07-21 | 南京驯鹿医疗技术有限公司 | 靶向cd5的全人源抗体 |
WO2022178040A1 (en) * | 2021-02-16 | 2022-08-25 | City Of Hope | Truncated domain iv egfr and uses thereof |
WO2022177677A1 (en) * | 2021-02-16 | 2022-08-25 | City Of Hope | Truncated domain iv egfr and uses thereof |
JP2024510898A (ja) | 2021-02-25 | 2024-03-12 | ライエル・イミュノファーマ・インコーポレイテッド | Ror1を標的とするキメラ抗原受容体 |
AU2022226655A1 (en) | 2021-02-25 | 2023-07-27 | Lyell Immunopharma, Inc. | Codon-optimized nucleotide sequences encoding an ap-1 transcription factor |
WO2022187289A1 (en) | 2021-03-01 | 2022-09-09 | Exuma Biotech Corp. | Methods and compositions for the delivery of retroviral particles |
CN117693508A (zh) | 2021-03-03 | 2024-03-12 | 朱诺治疗学股份有限公司 | T细胞疗法和dgk抑制剂的组合 |
CA3208944A1 (en) | 2021-03-22 | 2022-09-29 | Edith NALBANDIAN | Method to assess potency of viral vector particles |
CA3210581A1 (en) | 2021-03-22 | 2022-09-29 | Neil HAIG | Methods of determining potency of a therapeutic cell composition |
BR112023019847A2 (pt) | 2021-03-29 | 2023-11-07 | Juno Therapeutics Inc | Métodos para dosagem e tratamento com uma combinação de uma terapia com inibidor de ponto de verificação e uma terapia com célula t car |
AU2022252220A1 (en) | 2021-03-29 | 2023-10-12 | Juno Therapeutics, Inc. | Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma |
IL307612A (en) | 2021-04-16 | 2023-12-01 | Celgene Corp | Combined therapies with BCMA-directed T-cell therapy |
CA3214280A1 (en) | 2021-04-16 | 2022-10-20 | Julie Ann RYTLEWSKI | T cell therapy in patients who have had prior stem cell transplant |
WO2022232612A1 (en) | 2021-04-29 | 2022-11-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Lassa virus-specific nanobodies and methods of their use |
CN117916256A (zh) | 2021-05-06 | 2024-04-19 | 朱诺治疗学有限公司 | 用于刺激和转导t细胞的方法 |
CN117500831A (zh) | 2021-06-09 | 2024-02-02 | 美国政府(由卫生和人类服务部的部长所代表) | 用于治疗实体瘤的靶向pd-l1的跨物种单结构域抗体 |
WO2023076881A1 (en) | 2021-10-26 | 2023-05-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting the s2 subunit of sars-cov-2 spike protein |
US20230313138A1 (en) | 2021-10-28 | 2023-10-05 | Lyell Immunopharma, Inc. | Methods for culturing cells expressing c-jun |
IL312204A (en) | 2021-10-28 | 2024-06-01 | Lyell Immunopharma Inc | Methods for culturing cells expressing ROR1 binding protein |
WO2023081715A1 (en) | 2021-11-03 | 2023-05-11 | Viracta Therapeutics, Inc. | Combination of car t-cell therapy with btk inhibitors and methods of use thereof |
WO2023081735A1 (en) | 2021-11-03 | 2023-05-11 | Celgene Corporation | Chimeric antigen receptors specific for b-cell maturation antigen for use in treating myeloma |
WO2023086829A1 (en) | 2021-11-09 | 2023-05-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Igg4 hinge-containing chimeric antigen receptors targeting glypican-3 (gpc3) and use thereof |
WO2023147515A1 (en) | 2022-01-28 | 2023-08-03 | Juno Therapeutics, Inc. | Methods of manufacturing cellular compositions |
WO2023154890A2 (en) * | 2022-02-11 | 2023-08-17 | Fred Hutchinson Cancer Center | Chimeric antigen receptors binding steap1 |
WO2023158986A1 (en) | 2022-02-15 | 2023-08-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cd28 hinge and transmembrane containing chimeric antigen receptors targeting gpc2 and use thereof |
WO2023164440A1 (en) | 2022-02-22 | 2023-08-31 | Juno Therapeutics, Inc. | Proteinase 3 (pr3) chimeric autoantibody receptor t cells and related methods and uses |
WO2023168305A1 (en) | 2022-03-01 | 2023-09-07 | Exuma Biotech Corp. | Viral particles with membrane-bound hyaluronidase |
WO2023215416A1 (en) * | 2022-05-04 | 2023-11-09 | Earli Inc. | Methods using surface-expressable activatable epitopes to localize and/or treat diseased cells |
WO2023213969A1 (en) | 2022-05-05 | 2023-11-09 | Juno Therapeutics Gmbh | Viral-binding protein and related reagents, articles, and methods of use |
WO2023220641A2 (en) | 2022-05-11 | 2023-11-16 | Juno Therapeutics, Inc. | Methods and uses related to t cell therapy and production of same |
WO2023220655A1 (en) | 2022-05-11 | 2023-11-16 | Celgene Corporation | Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy |
WO2023230581A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Methods of manufacturing t cell therapies |
WO2023230548A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Method for predicting response to a t cell therapy |
WO2023250400A1 (en) | 2022-06-22 | 2023-12-28 | Juno Therapeutics, Inc. | Treatment methods for second line therapy of cd19-targeted car t cells |
WO2024006960A1 (en) | 2022-06-29 | 2024-01-04 | Juno Therapeutics, Inc. | Lipid nanoparticles for delivery of nucleic acids |
WO2024026490A1 (en) | 2022-07-28 | 2024-02-01 | Sqz Biotechnologies Company | Polynucleotides encoding linked antigens and uses thereof |
WO2024031091A2 (en) | 2022-08-05 | 2024-02-08 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for gprc5d and bcma |
WO2024044779A2 (en) | 2022-08-26 | 2024-02-29 | Juno Therapeutics, Inc. | Antibodies and chimeric antigen receptors specific for delta-like ligand 3 (dll3) |
WO2024050399A1 (en) | 2022-09-01 | 2024-03-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting hpv e6/e7 oncogenic peptide/mhc complexes |
WO2024054944A1 (en) | 2022-09-08 | 2024-03-14 | Juno Therapeutics, Inc. | Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing |
WO2024056809A1 (en) | 2022-09-15 | 2024-03-21 | Novartis Ag | Treatment of autoimmune disorders using chimeric antigen receptor therapy |
WO2024064952A1 (en) | 2022-09-23 | 2024-03-28 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells overexpressing c-jun |
WO2024064958A1 (en) | 2022-09-23 | 2024-03-28 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells |
WO2024077174A1 (en) | 2022-10-05 | 2024-04-11 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells |
WO2024097905A1 (en) | 2022-11-02 | 2024-05-10 | Celgene Corporation | Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy |
WO2024100604A1 (en) | 2022-11-09 | 2024-05-16 | Juno Therapeutics Gmbh | Methods for manufacturing engineered immune cells |
WO2024124132A1 (en) | 2022-12-09 | 2024-06-13 | Juno Therapeutics, Inc. | Machine learning methods for predicting cell phenotype using holographic imaging |
WO2024129778A2 (en) | 2022-12-13 | 2024-06-20 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for baff-r and cd19 and methods and uses thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003522525A (ja) | 1999-11-19 | 2003-07-29 | ノバルティス アクチエンゲゼルシャフト | 細胞表面選択マーカー遺伝子 |
WO2006009694A3 (en) | 2004-06-14 | 2006-10-12 | Imclone Sysetms Inc | Crystal of egfr extracellular domain and cetuximab fab fragment and uses thereof |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0590058T3 (da) | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
US5753462A (en) * | 1995-06-07 | 1998-05-19 | Zymogenetics, Inc. | Secretion leader trap cloning method |
US6790614B1 (en) * | 1999-11-19 | 2004-09-14 | Novartis Ag | Selectable cell surface marker genes |
WO2002077029A2 (en) * | 2000-11-07 | 2002-10-03 | City Of Hope | Cd19-specific redirected immune cells |
US7105221B2 (en) * | 2001-07-19 | 2006-09-12 | Toray Industries, Inc. | Circuit board, laminated member for circuit board, and method for making laminated member for circuit board |
US7955845B2 (en) * | 2001-11-20 | 2011-06-07 | Dana Farber Cancer Institute, Inc. | Modified antigen-presenting cells |
KR20140142311A (ko) * | 2003-06-27 | 2014-12-11 | 암젠 프레몬트 인코포레이티드 | 상피 성장 인자 수용체의 결실 돌연변이체 지향 항체 및 그 용도 |
AU2010315243B2 (en) | 2009-11-03 | 2016-08-25 | City Of Hope | Truncated epidermal growth factor receptor (EGFRt) for transduced T cell selection |
-
2010
- 2010-11-03 AU AU2010315243A patent/AU2010315243B2/en active Active
- 2010-11-03 EP EP19150829.0A patent/EP3527585B1/en active Active
- 2010-11-03 PL PL10829041T patent/PL2496698T3/pl unknown
- 2010-11-03 TR TR2019/04484T patent/TR201904484T4/tr unknown
- 2010-11-03 PT PT10829041T patent/PT2496698T/pt unknown
- 2010-11-03 CA CA2779526A patent/CA2779526C/en active Active
- 2010-11-03 ES ES10829041T patent/ES2717629T3/es active Active
- 2010-11-03 EP EP10829041.2A patent/EP2496698B1/en active Active
- 2010-11-03 EP EP22151210.6A patent/EP4049674A1/en active Pending
- 2010-11-03 ES ES19150829T patent/ES2911246T3/es active Active
- 2010-11-03 WO PCT/US2010/055329 patent/WO2011056894A2/en active Application Filing
- 2010-11-03 SI SI201031870T patent/SI2496698T1/sl unknown
- 2010-11-03 JP JP2012537974A patent/JP5956342B2/ja active Active
- 2010-11-03 DK DK10829041.2T patent/DK2496698T3/en active
- 2010-11-03 HU HUE10829041 patent/HUE044461T2/hu unknown
-
2012
- 2012-05-03 US US13/463,247 patent/US8802374B2/en active Active
-
2014
- 2014-07-24 US US14/340,512 patent/US9580685B2/en active Active
-
2016
- 2016-06-16 JP JP2016120180A patent/JP6267278B2/ja active Active
- 2016-11-24 AU AU2016262738A patent/AU2016262738A1/en not_active Abandoned
-
2017
- 2017-02-13 US US15/431,248 patent/US10100281B2/en active Active
- 2017-08-30 JP JP2017165623A patent/JP6499245B2/ja active Active
-
2018
- 2018-10-15 US US16/160,944 patent/US11155783B2/en active Active
- 2018-11-12 AU AU2018263993A patent/AU2018263993A1/en not_active Abandoned
-
2019
- 2019-03-14 JP JP2019046818A patent/JP6753975B2/ja active Active
- 2019-03-22 HR HRP20190556TT patent/HRP20190556T1/hr unknown
-
2020
- 2020-08-20 JP JP2020139041A patent/JP7116126B6/ja active Active
-
2021
- 2021-05-21 AU AU2021203288A patent/AU2021203288B2/en active Active
- 2021-10-22 US US17/507,996 patent/US20220041986A1/en active Pending
-
2022
- 2022-07-28 JP JP2022120718A patent/JP7320656B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003522525A (ja) | 1999-11-19 | 2003-07-29 | ノバルティス アクチエンゲゼルシャフト | 細胞表面選択マーカー遺伝子 |
WO2006009694A3 (en) | 2004-06-14 | 2006-10-12 | Imclone Sysetms Inc | Crystal of egfr extracellular domain and cetuximab fab fragment and uses thereof |
Non-Patent Citations (1)
Title |
---|
Annu. Rev. Biophys.,2008年,Vol. 37,pp. 353-373 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7116126B6 (ja) | 形質導入T細胞選択のためのトランケート上皮増殖因子レセプタ(EGFRt) | |
JP7402933B2 (ja) | 導入遺伝子の遺伝子タグおよびその使用方法 | |
EP2884999B1 (en) | Method and compositions for cellular immunotherapy | |
KR20210019993A (ko) | Τ 세포 수용체 및 이를 발현하는 조작된 세포 | |
RU2822461C1 (ru) | Трансгенные генетические метки и способы применения | |
BR112016023507B1 (pt) | Polipeptídeo isolado que compreende um domínio extracelular de um polipeptídeo her2 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200918 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200918 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210831 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211130 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220131 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220228 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220628 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220728 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7116126 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |