JP7428663B2 - いくつかの多重抗原の標的用の逆ユニバーサルキメラ抗原受容体を発現する免疫細胞ならびにその製造方法ならびに癌、感染症および自己免疫疾患を治療するためのその使用 - Google Patents
いくつかの多重抗原の標的用の逆ユニバーサルキメラ抗原受容体を発現する免疫細胞ならびにその製造方法ならびに癌、感染症および自己免疫疾患を治療するためのその使用 Download PDFInfo
- Publication number
- JP7428663B2 JP7428663B2 JP2020569080A JP2020569080A JP7428663B2 JP 7428663 B2 JP7428663 B2 JP 7428663B2 JP 2020569080 A JP2020569080 A JP 2020569080A JP 2020569080 A JP2020569080 A JP 2020569080A JP 7428663 B2 JP7428663 B2 JP 7428663B2
- Authority
- JP
- Japan
- Prior art keywords
- cell
- receptor
- domain
- adapter module
- nucleic acid
- 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
- 210000002865 immune cell Anatomy 0.000 title claims description 72
- 239000000427 antigen Substances 0.000 title claims description 56
- 108091007433 antigens Proteins 0.000 title claims description 56
- 102000036639 antigens Human genes 0.000 title claims description 56
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 title claims description 41
- 230000002441 reversible effect Effects 0.000 title claims description 32
- 206010028980 Neoplasm Diseases 0.000 title claims description 28
- 238000000034 method Methods 0.000 title description 38
- 201000011510 cancer Diseases 0.000 title description 14
- 238000004519 manufacturing process Methods 0.000 title description 12
- 208000023275 Autoimmune disease Diseases 0.000 title description 8
- 230000008685 targeting Effects 0.000 title description 6
- 208000035473 Communicable disease Diseases 0.000 title description 5
- 210000004027 cell Anatomy 0.000 claims description 102
- 230000027455 binding Effects 0.000 claims description 82
- 150000007523 nucleic acids Chemical class 0.000 claims description 69
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 61
- 108090000623 proteins and genes Proteins 0.000 claims description 57
- 102000004169 proteins and genes Human genes 0.000 claims description 50
- 241000282414 Homo sapiens Species 0.000 claims description 48
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 38
- 108020004707 nucleic acids Proteins 0.000 claims description 37
- 102000039446 nucleic acids Human genes 0.000 claims description 37
- 238000002360 preparation method Methods 0.000 claims description 32
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 claims description 29
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 claims description 29
- 239000012634 fragment Substances 0.000 claims description 24
- 239000003446 ligand Substances 0.000 claims description 20
- 239000013598 vector Substances 0.000 claims description 20
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 15
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 15
- 108091008874 T cell receptors Proteins 0.000 claims description 15
- 230000011664 signaling Effects 0.000 claims description 15
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 12
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 12
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 12
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 12
- 102100036735 Prostate stem cell antigen Human genes 0.000 claims description 12
- 101710120463 Prostate stem cell antigen Proteins 0.000 claims description 12
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 12
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 claims description 11
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 11
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 11
- 230000001086 cytosolic effect Effects 0.000 claims description 10
- 102000005962 receptors Human genes 0.000 claims description 10
- 108020003175 receptors Proteins 0.000 claims description 10
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 9
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 9
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 9
- 102000001301 EGF receptor Human genes 0.000 claims description 9
- 108060006698 EGF receptor Proteins 0.000 claims description 9
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 9
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 9
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 8
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 8
- 230000028993 immune response Effects 0.000 claims description 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 8
- 230000019491 signal transduction Effects 0.000 claims description 8
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 7
- 101150029707 ERBB2 gene Proteins 0.000 claims description 7
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 claims description 7
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 7
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 7
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 7
- 208000032839 leukemia Diseases 0.000 claims description 7
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims description 6
- 108010060374 FSH Receptors Proteins 0.000 claims description 6
- 101000972485 Homo sapiens Lupus La protein Proteins 0.000 claims description 6
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 102000018697 Membrane Proteins Human genes 0.000 claims description 6
- 108010052285 Membrane Proteins Proteins 0.000 claims description 6
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 5
- 102100027207 CD27 antigen Human genes 0.000 claims description 5
- 108060001253 CD99 Proteins 0.000 claims description 5
- 102000024905 CD99 Human genes 0.000 claims description 5
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims description 5
- 108010087819 Fc receptors Proteins 0.000 claims description 5
- 102000009109 Fc receptors Human genes 0.000 claims description 5
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 5
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 5
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 claims description 5
- 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 5
- 102000015728 Mucins Human genes 0.000 claims description 5
- 108010063954 Mucins Proteins 0.000 claims description 5
- 102000007999 Nuclear Proteins Human genes 0.000 claims description 5
- 108010089610 Nuclear Proteins Proteins 0.000 claims description 5
- 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 claims description 5
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 5
- 210000005260 human cell Anatomy 0.000 claims description 5
- 102100023635 Alpha-fetoprotein Human genes 0.000 claims description 4
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 4
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 4
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 4
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 4
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 claims description 4
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims description 4
- 102100022742 Lupus La protein Human genes 0.000 claims description 4
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 claims description 4
- 108010085220 Multiprotein Complexes Proteins 0.000 claims description 4
- 102000007474 Multiprotein Complexes Human genes 0.000 claims description 4
- 102000000812 NK Cell Lectin-Like Receptor Subfamily K Human genes 0.000 claims description 4
- 108010001657 NK Cell Lectin-Like Receptor Subfamily K Proteins 0.000 claims description 4
- 101001039269 Rattus norvegicus Glycine N-methyltransferase Proteins 0.000 claims description 4
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 4
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 4
- 102000003675 cytokine receptors Human genes 0.000 claims description 4
- 108010057085 cytokine receptors Proteins 0.000 claims description 4
- 210000000822 natural killer cell Anatomy 0.000 claims description 4
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 claims description 3
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 3
- 102100024217 CAMPATH-1 antigen Human genes 0.000 claims description 3
- 102100038078 CD276 antigen Human genes 0.000 claims description 3
- 102100032912 CD44 antigen Human genes 0.000 claims description 3
- 108010065524 CD52 Antigen Proteins 0.000 claims description 3
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 3
- 101150039808 Egfr gene Proteins 0.000 claims description 3
- 108091008815 Eph receptors Proteins 0.000 claims description 3
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 claims description 3
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 3
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 claims description 3
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 3
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims description 3
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 claims description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 3
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 claims description 3
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 3
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims description 3
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 claims description 3
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 3
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 claims description 3
- 102000017578 LAG3 Human genes 0.000 claims description 3
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 claims description 3
- 108050008953 Melanoma-associated antigen Proteins 0.000 claims description 3
- 108091008877 NK cell receptors Proteins 0.000 claims description 3
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 claims description 3
- 108090000028 Neprilysin Proteins 0.000 claims description 3
- 102000003729 Neprilysin Human genes 0.000 claims description 3
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 3
- 230000006044 T cell activation Effects 0.000 claims description 3
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 3
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 3
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 claims description 3
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 3
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 3
- 102100026497 Zinc finger protein 654 Human genes 0.000 claims description 3
- 102000034337 acetylcholine receptors Human genes 0.000 claims description 3
- 230000001605 fetal effect Effects 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims description 3
- 230000009258 tissue cross reactivity Effects 0.000 claims description 3
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 3
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 claims description 2
- 102000003846 Carbonic anhydrases Human genes 0.000 claims description 2
- 108090000209 Carbonic anhydrases Proteins 0.000 claims description 2
- 102100034231 Cell surface A33 antigen Human genes 0.000 claims description 2
- 101710165668 Cell surface A33 antigen Proteins 0.000 claims description 2
- 108010059480 Chondroitin Sulfate Proteoglycans Proteins 0.000 claims description 2
- 102000005598 Chondroitin Sulfate Proteoglycans Human genes 0.000 claims description 2
- 102000050554 Eph Family Receptors Human genes 0.000 claims description 2
- 102000013446 GTP Phosphohydrolases Human genes 0.000 claims description 2
- 108091006109 GTPases Proteins 0.000 claims description 2
- 108060003951 Immunoglobulin Proteins 0.000 claims description 2
- 101710112634 Interleukin-13 receptor subunit alpha-2 Proteins 0.000 claims description 2
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 claims description 2
- 102000019040 Nuclear Antigens Human genes 0.000 claims description 2
- 108010051791 Nuclear Antigens Proteins 0.000 claims description 2
- 102000042463 Rho family Human genes 0.000 claims description 2
- 108091078243 Rho family Proteins 0.000 claims description 2
- 108010002687 Survivin Proteins 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 102000006815 folate receptor Human genes 0.000 claims description 2
- 108020005243 folate receptor Proteins 0.000 claims description 2
- 102000018358 immunoglobulin Human genes 0.000 claims description 2
- 102000002467 interleukin receptors Human genes 0.000 claims description 2
- 108010093036 interleukin receptors Proteins 0.000 claims description 2
- 210000000265 leukocyte Anatomy 0.000 claims description 2
- 210000003289 regulatory T cell Anatomy 0.000 claims description 2
- 102100027627 Follicle-stimulating hormone receptor Human genes 0.000 claims 2
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 claims 1
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 102000012406 Carcinoembryonic Antigen Human genes 0.000 claims 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 claims 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims 1
- 101000916059 Homo sapiens C-X-C chemokine receptor type 2 Proteins 0.000 claims 1
- 102000007066 Prostate-Specific Antigen Human genes 0.000 claims 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 30
- 239000012636 effector Substances 0.000 description 25
- 238000011282 treatment Methods 0.000 description 16
- 108010076504 Protein Sorting Signals Proteins 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 10
- -1 targeting signal Proteins 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 108010022394 Threonine synthase Proteins 0.000 description 7
- 102000004419 dihydrofolate reductase Human genes 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 230000015861 cell surface binding Effects 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 102000027596 immune receptors Human genes 0.000 description 6
- 108091008915 immune receptors Proteins 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 108010075254 C-Peptide Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- 102000018343 Follicle stimulating hormone receptors Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 102100034349 Integrase Human genes 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 108700010039 chimeric receptor Proteins 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 229920002704 polyhistidine Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108700012439 CA9 Proteins 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 3
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 3
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102100026094 C-type lectin domain family 12 member A Human genes 0.000 description 2
- 101710188619 C-type lectin domain family 12 member A Proteins 0.000 description 2
- 238000011357 CAR T-cell therapy Methods 0.000 description 2
- 101150074155 DHFR gene Proteins 0.000 description 2
- 101710121417 Envelope glycoprotein Proteins 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 2
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 2
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 2
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 2
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 2
- 101710112663 Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108010052781 Interleukin-3 Receptor alpha Subunit Proteins 0.000 description 2
- 102000018883 Interleukin-3 Receptor alpha Subunit Human genes 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 102000000704 Interleukin-7 Human genes 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins 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
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 2
- 102100034256 Mucin-1 Human genes 0.000 description 2
- 102100023123 Mucin-16 Human genes 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- RMINQIRDFIBNLE-NNRWGFCXSA-N O-[N-acetyl-alpha-neuraminyl-(2->6)-N-acetyl-alpha-D-galactosaminyl]-L-serine Chemical compound O1[C@H](OC[C@H](N)C(O)=O)[C@H](NC(=O)C)[C@@H](O)[C@@H](O)[C@H]1CO[C@@]1(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C1 RMINQIRDFIBNLE-NNRWGFCXSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000009328 Perro Species 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108091027981 Response element Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 238000010459 TALEN Methods 0.000 description 2
- 108700012411 TNFSF10 Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 2
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 201000000053 blastoma Diseases 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000007975 buffered saline Substances 0.000 description 2
- 239000004067 bulking agent Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 201000008184 embryoma Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 102000052972 human La Human genes 0.000 description 2
- 102000050327 human TNFRSF9 Human genes 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000004068 intracellular signaling Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 208000003747 lymphoid leukemia Diseases 0.000 description 2
- 102000006240 membrane receptors Human genes 0.000 description 2
- 108020004084 membrane receptors Proteins 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000000242 pagocytic effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000004986 primary T-cell Anatomy 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 210000003370 receptor cell Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 208000000649 small cell carcinoma Diseases 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- FFILOTSTFMXQJC-QCFYAKGBSA-N (2r,4r,5s,6s)-2-[3-[(2s,3s,4r,6s)-6-[(2s,3r,4r,5s,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2r,3s,4r,5r,6r)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(e)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hy Chemical compound O[C@@H]1[C@@H](O)[C@H](OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 FFILOTSTFMXQJC-QCFYAKGBSA-N 0.000 description 1
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- 102000008482 12E7 Antigen Human genes 0.000 description 1
- 108010020567 12E7 Antigen Proteins 0.000 description 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- QZDDFQLIQRYMBV-UHFFFAOYSA-N 2-[3-nitro-2-(2-nitrophenyl)-4-oxochromen-8-yl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(C=2[N+]([O-])=O)=O)=C1OC=2C1=CC=CC=C1[N+]([O-])=O QZDDFQLIQRYMBV-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 206010068873 Adenosquamous cell carcinoma Diseases 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 102100022749 Aminopeptidase N Human genes 0.000 description 1
- 241001128034 Amphotropic murine leukemia virus Species 0.000 description 1
- 101710145634 Antigen 1 Proteins 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108010049990 CD13 Antigens Proteins 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 201000004085 CLL/SLL Diseases 0.000 description 1
- 238000010453 CRISPR/Cas method Methods 0.000 description 1
- 101100355609 Caenorhabditis elegans rae-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 101100044298 Drosophila melanogaster fand gene Proteins 0.000 description 1
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 1
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
- 108010055182 EphA5 Receptor Proteins 0.000 description 1
- 102000056118 Ephrin receptor family Human genes 0.000 description 1
- 102100021605 Ephrin type-A receptor 5 Human genes 0.000 description 1
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 1
- 102000044591 ErbB-4 Receptor Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 101150064015 FAS gene Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 101710177291 Gag polyprotein Proteins 0.000 description 1
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
- 108010058940 Glutamyl Aminopeptidase Proteins 0.000 description 1
- 102000006485 Glutamyl Aminopeptidase Human genes 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241001326189 Gyrodactylus prostae Species 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 description 1
- 101000938391 Homo sapiens Transmembrane protein Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 1
- 101000620751 Homo sapiens mRNA export factor RAE1 Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000714192 Human spumaretrovirus Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 208000017817 Immunodeficiency-associated lymphoproliferative disease Diseases 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 102000004559 Interleukin-13 Receptors Human genes 0.000 description 1
- 108010017511 Interleukin-13 Receptors Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 102400000704 Intracellular domain 1 Human genes 0.000 description 1
- 101800001559 Intracellular domain 1 Proteins 0.000 description 1
- 102400000705 Intracellular domain 2 Human genes 0.000 description 1
- 101800001556 Intracellular domain 2 Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- 230000006051 NK cell activation Effects 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 208000008846 Neurocytoma Diseases 0.000 description 1
- 102100028762 Neuropilin-1 Human genes 0.000 description 1
- 108090000772 Neuropilin-1 Proteins 0.000 description 1
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- 101100335198 Pneumocystis carinii fol1 gene Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108010029157 Sialic Acid Binding Ig-like Lectin 2 Proteins 0.000 description 1
- 102000001613 Sialic Acid Binding Ig-like Lectin 2 Human genes 0.000 description 1
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 1
- 102000001555 Sialic Acid Binding Ig-like Lectin 3 Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000032383 Soft tissue cancer Diseases 0.000 description 1
- 101800001707 Spacer peptide Proteins 0.000 description 1
- 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
- 108010092867 Transforming Growth Factor beta Receptors Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 206010045170 Tumour lysis syndrome Diseases 0.000 description 1
- 229940127174 UCHT1 Drugs 0.000 description 1
- 101150042088 UL16 gene Proteins 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
- 108700025700 Wilms Tumor Genes Proteins 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000006786 activation induced cell death Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 101150063416 add gene Proteins 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000015230 aggressive NK-cell leukemia Diseases 0.000 description 1
- SRHNADOZAAWYLV-XLMUYGLTSA-N alpha-L-Fucp-(1->2)-beta-D-Galp-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](NC(C)=O)[C@H](O)O[C@@H]2CO)O[C@H]2[C@H]([C@H](O)[C@H](O)[C@H](C)O2)O)O[C@H](CO)[C@H](O)[C@@H]1O SRHNADOZAAWYLV-XLMUYGLTSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 206010052015 cytokine release syndrome Diseases 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 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 1
- 239000006185 dispersion Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 201000008361 ganglioneuroma Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 108010017007 glucose-regulated proteins Proteins 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 102100022885 mRNA export factor RAE1 Human genes 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 239000012516 mab select resin Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 201000000638 mature B-cell neoplasm Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000011294 monotherapeutic Methods 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010915 neoplasm of mature B-cells Diseases 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910001453 nickel ion Inorganic materials 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000002820 pancreatoblastoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 208000010626 plasma cell neoplasm Diseases 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 108010089520 pol Gene Products Proteins 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000010380 tumor lysis syndrome Diseases 0.000 description 1
- 208000010576 undifferentiated carcinoma Diseases 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 201000011531 vascular cancer Diseases 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4613—Natural-killer cells [NK or NK-T]
-
- 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
- A61K39/4614—Monocytes; Macrophages
-
- 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
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
-
- 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
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46433—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- 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
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/55—IL-2
-
- 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
- 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
- C07K14/70521—CD28, CD152
-
- 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
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- 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
Description
本発明の方法で使用されるエフェクター細胞は、治療される疾患および治療を行うために有効な方法に依存した選択で、自己由来、同系または異系であってよい。この方法で使用することができるエレクター細胞の適切な集団は、細胞溶解活性、食細胞活性または免疫抑制活性を有する任意の免疫細胞、例えば制御性T細胞を含むT細胞、NK細胞およびマクロファージを含む。一形態では、エフェクター細胞は、特定のHLAバッググラウンドに由来し、自己または同種系内で利用される。エフェクター細胞は、治療される被験者の腫瘍外植体または治療される被験者の腫瘍内細胞を含めた任意の供給源から単離することができる。一実施態様では、エフェクター細胞は、RevCARを発現するためのそれぞれの細胞の遺伝子操作の前または後に、多能性または多分化能性の幹細胞または原始細胞からのインビトロ分化により生成されてよい。以後、「エフェクター細胞」という用語は、その細胞表面上にRevCARを発現するように遺伝子改変された任意の種類の上述の免疫細胞を指す。
本発明の方法で使用されるエフェクター細部により発現されるRevCARは、抗原特異的な方法で、RevCARを発現する免疫細胞の、モジュール式で、極めてフレキシブルでかつ厳密に制御可能な再標的化を可能にする。この方法で使用されるRevCARのための唯一の要件は、(i)その細胞表面ペプチドエピトープタグを介してRevCARが、アダプターモジュールに接合することができる特別なタグ結合部位に対して結合特異性を有し、標的細胞の細胞表面タンパク質または細胞外構造に次々に結合すること、および(ii)免疫細胞がRevCARを発現するように操作することができることである。
アダプターモジュールは、特定のヒト表面タンパク質またはタンパク質複合体に特異的な結合部位と、本発明によるRevCAR受容体の細胞表面ペプチドエピトープに結合する結合部位とから構築される。アダプターモジュールは、RevCAR発現エフェクター細胞の投与前、投与と同時、または投与後に被験者に投与される。あるいは、RevCAR発現エフェクター細胞は、レシピエントに注入する前に、アダプターモジュールで装飾されていてよい。アダプターモジュールの潜在的結合部位は、CD2、CD3、CD4、CD8、CD10、CD19、CD20、CD22、CD25、CD23、CD30、CD33、CD38、CD44、CD52、CD90、CD99、CD123、CD223、CD269(B細胞成熟抗原、BCMA)、CD274、CD276、CD279およびCD366のような表面抗原に結合する抗体またはその抗体のフラグメント、上皮成長因子受容体ファミリーのメンバー(ErbB1、ErbB2、ErbB3、ErbB4およびそれらの変異体)、上皮成長因子受容体(EGFR)、腫瘍壊死因子受容体スーパーファミリーのメンバー、エフリン受容体ファミリーのメンバー(EphA1-10、EphB1-6)、いわゆる前立腺特異的抗原(例えば前立腺幹細胞抗原PSCA、前立腺特異的膜抗原PSMA)、胚性抗原(例えば癌胚性抗原CEA、胎児アセチルコリン受容体)、血管内皮増殖因子ファミリーのメンバー(VEGFR1-3)、上皮細胞接着分子EpCAM、アルファフェトプロテインAFP、ムチンタンパク質ファミリーのメンバー(例えばMUC1、MUC16)、卵胞刺激ホルモン受容体(FSHR)、ヒト高分子量メラノーマ関連抗原(HMW-MAA)、葉酸結合タンパク質FBP、a-葉酸受容体、NKG2D受容体のリガンド、サイトカイン受容体[例えばIL-8Rα(CXCR1)、IL-8Rβ(CXCR2)、IL-11Rα、IL-11Rβ、IL-13Rα1および2、CXCR4]、上皮糖タンパク質ファミリーのメンバー(例えばEGP-2、EGP-4)、ジアシアロガングリオシド(例えばGD2、GD3)、炭酸脱水酵素ファミリーのメンバー(例えばCAIX)、炭水化物抗原ファミリーのメンバー(例えばLey)、Notchリガンド(例えばデルタ様1および4)、メラノーマ関連コンドロイチン硫酸プロテオグリカン(MCSP)、糖タンパク質A33、および腫瘍特異的グリカン[例えばセリンまたはスレオニン連結Nアセチルガラクトサミン(Tn)またはシアリル-Tnのような誘導体](上述のタンパク質およびタンパク質ファミリーの変異体を含む)を含むが、これらに限定されるものではない。さらに、アダプターモジュールの結合部位は、La/SSB抗原のような細胞質抗原または核抗原、GTPaseのRhoファミリーのメンバー、高移動度タンパク質のメンバーなどに結合する抗体またはその抗体のフラグメントを含むが、これらに限定されるものではない。同様に、アダプターモジュールの結合部位は、T細胞受容体(TCR)のアルファ鎖およびベータ鎖またはガンマ鎖およびデルタ鎖またはそれらのフラグメントから構成されていることができる。このようなTCR由来の結合部位は、ヒト白血球抗原クラス(HLA)IおよびIIタンパク質複合体により提示されるペプチドを認識しかつそのペプチドに結合する。例は、EGFRファミリー、サバイビン、sry様高移動度box(SOX)タンパク質ファミリー、メラノーマ関連抗原(例えば自己免疫原性癌/精巣抗原NY-ESO-1)、メラノーマ抗原ファミリーAのメンバー(MAGEA)、メラノーマにおいて優先的に発現する抗原(PRAME)、および白血病関連抗原(例えばウィルムス腫瘍遺伝子1WT1)のようなタンパク質に由来するペプチドに特異的なTCRであるが、これらに限定されるものではない。アダプターモジュールの結合部位は、タンパク質およびタンパク質複合体に対するリガンド、さらに受容体、またはその受容体のフラグメントとも言われるものを含むこともできる。このようなリガンドは、サイトカイン受容体(例えばIL-13受容体)、NKG2D受容体のリガンド、EGFRファミリーメンバーに対するリガンド、PD-1、CTLA-4、リンパ球活性化遺伝子3(LAG-3)またはT細胞免疫グロブリンおよびムチンドメイン含有3(TIM-3)のようなチェックポイント分子のリガンド、または自己反応性TCRに結合してもよいが、これらに限定されるものではない。さらに、標的結合部位は、化学反応(つまりクリックケミストリー)を介してタグ結合部位に融合される化学合成されたペプチド誘導体であることもできる。好ましい実施態様では、膜受容体に対する結合特異性を有するペプチドは、CD2、CD3、CD4、CD8、CD10、CD19、CD20、CD22、CD25、CD23、CD30、CD33、CD38、CD44、CD52、CD90、CD99、CD123、CD223、CD269、CD274、CD276、CD279およびCD366、インターロイキン受容体、特に好ましくはIL-8Rα(CXCR1)、IL-8Rβ(CXCR2)、IL-11Rα、IL-11Rβ、IL-13Rα1および2、CXCR4;c-Met、形質転換成長因子β受容体、erbB1、erbB2、erbB3、erbB4およびこれらの変異体、腫瘍壊死因子受容体スーパーファミリーのメンバー、エフリン受容体、特に好ましくはEphA1-10、EphA5またはEphB1-6;前立腺幹細胞抗原(PSCA)、前立腺特異的膜抗原(PSMA)、癌胚性抗原(CEA)、胎児アセチルコリン受容体、腫瘍胎児抗原、腫瘍特異的グリカン[例えばセリンまたはスレオニン連結Nアセチルガラクトサミン(Tn)またはシアリル-Tnのような誘導体];VEGFR1、VEGFR2またはVEGFR3、ニューロピリン-1、上皮細胞接着分子(EpCAM)、上皮成長因子受容体(EGFR)、アルファフェトプロテイン(AFP)、ムチン、特に好ましくはMUC1、MUC16またはMUC18;卵胞刺激ホルモン受容体(FSHR)、ヒト高分子量メラノーマ関連抗原(HMW-MAA)、葉酸結合タンパク質(FBP)、葉酸受容体、NKG2D、主要組織適合性複合体(MHC)クラスI分子、特に好ましくはMHCクラスI鎖関連遺伝子A(MICA)またはB(MICB)、UL16結合タンパク質(ULPB)1、ULPB2、ULPB3、リボ核酸搬出1(Rae-1)ファミリーメンバーまたは組織適合性60(H-60);シャペロンおよびヒートショックタンパク質、特に好ましくはヒートショックタンパク質(HSP)90または78kDaグルコース調節タンパク質(GRP78);EGP-2またはEGP-4、ジアシアロガングリオシド2(GD2)またはGD3、炭酸脱水酵素9(CAIX)、ルイスY(LeY)、C型レクチン様分子-1(CLL-1)、腫瘍壊死因子関連アポトーシス誘導リガンド(TRAIL)受容体、アポトーシス抗原1(APO-1、Fas、CD95)、ケラチンファミリーまたはインテグリンのメンバー、特に好ましくはavβ3またはavβ5、アミノペプチダーゼA、アミノペプチダーゼNまたは神経/グリア抗原2(NG2)から選択される膜受容体に対する結合特異性を有する。
- 一つまたはより多くの逆ユニバーサルキメラ抗原受容体を発現するように遺伝子改変されたエフェクター細胞の有効量を哺乳類に投与し、ここで、逆ユニバーサルキメラ抗原受容体は、三つのドメインを有し、第一のドメインは、ペプチドエピトープタグであり、第二のドメインは、細胞外ヒンジおよび膜貫通ドメインであり、第三のドメインは、シグナル伝達ドメインであり、タグは、可溶性アダプターモジュールを作製するために適した結合ドメインにより認識される(図2)。
ここで、アダプターモジュールは、逆ユニバーサルキメラ抗原受容体発現エフェクター細胞の投与前、投与と同時、または投与後に被験者に投与される。
本発明の実施態様では、免疫細胞は、多様な方法によりRevCARを発現するように遺伝子操作されてよい。一般に、RevCARをコードするポリヌクレオチドベクターおよび遺伝子操作された免疫細胞内でのその発現を確実にするために必要な全ての要素が、細胞内に移入される。ベクターの移入は、以下に限定されるものではないが、核酸のエレクトロポレーションもしくはトランスフェクションによるか、または以下に限定されるものではないが、アデノウイルス、アデノ関連ウイルス、レトロウイルス、フォーミーウイルスまたはレンチウイルスのウイルス遺伝子移入のようなウイルスベクター系の補助により行うことができる。
5′LTR:5′長末端反復、PBS:プライマー結合サイト、Ψ:パッケージングシグナル、RRE:Rev応答エレメント、cPPT/CTS:(中央ポリプリン域/中央終止配列、PEF1α:ヒト伸長因子1アルファプロモーター、MCS:マルチクローニングサイト、IRES:内部リボソーム進入サイト、ZsGreen1:ヒトコドン最適化部位、WPRE:ウッドチャック肝炎ウイルス転写後調節エレメント、3′LTR:3′長末端反復、pUC:複製の起点、Ampr:アンピシリン耐性遺伝子;β-ラクタマーゼ。
アダプターモジュールは、特定のヒト細胞表面タンパク質またはタンパク質複合体に特異的な結合部位およびRevCARの細胞表面ペプチドエピトープタグに対して指向するタグ結合ドメインの、二つのドメインを有する。アダプターモジュールは、当業者に公知の技術により生産することができる。これらの技術は、原核細胞または真核細胞内での組換発現、ポリペプチド鎖の人工合成または化学合成を含むが、これらに限定されるものではない。
一つのアダプターモジュールまたは一つより多い、例えば二つ、三つ、四つまたはそれより多いアダプターモジュールは、当業者に公知の技術を用いて被験者に投与するために調製されてよい。
Claims (20)
- 逆ユニバーサルキメラ抗原受容体をコードする核酸において、前記受容体は、三つのドメインを有し、
- 第一のドメインは、ペプチドエピトープタグであり、前記ペプチドエピトープタグは、配列番号28または29によるヒト核タンパク質由来の短い線状エピトープであり、
- 第二のドメインは、細胞外ヒンジおよび膜貫通ドメインであり、かつ
- 第三のドメインは、シグナル伝達ドメインである、
逆ユニバーサルキメラ抗原受容体をコードする核酸。 - 配列番号3または11によるペプチドエピトープタグをコードする核酸を含む、請求項1に記載の核酸。
- 前記ヒンジおよび膜貫通ドメインは、ヒトCD28分子のヒンジおよび膜貫通ドメイン、CD8a鎖、NK細胞受容体、DAP12、Fc受容体または抗体の定常領域の一部、ならびにそれらのヒンジと膜貫通ドメインとの種々の組合せから選択され、前記ヒンジ領域は、細胞外領域の一部である、請求項1または2に記載の核酸。
- 前記シグナル伝達ドメインは、CD28、CD137(41BB)、CD134(OX40)、DAP10およびCD27の細胞質領域、プログラム細胞死-1(PD-1)、細胞障害性Tリンパ球抗原4(CTLA-4)ならびにCD3鎖、DAP12およびT細胞活性化を誘導するFc受容体の細胞質領域から選択され、前記シグナル伝達ドメインおよび前記細胞質領域は、シグナリングドメインである、請求項1から3までのいずれかに記載の核酸。
- 配列番号24から27までの配列の一つによる逆ユニバーサルキメラ抗原受容体をコードする、請求項1から4までのいずれかに記載の核酸。
- 前記受容体は、第四のドメインを有し、前記第四のドメインは、前記受容体の細胞外部分内の短いペプチドリンカーである、請求項1から4までのいずれかに記載の核酸。
- 配列番号1、8、10または12の配列の一つによる、請求項1から5までのいずれかに記載の核酸。
- 特定のヒト細胞表面タンパク質またはタンパク質複合体に特異的な結合部位と、請求項1から7までのいずれか一項に記載の逆ユニバーサルキメラ抗原受容体のペプチドエピトープタグに対して指向するタグ結合ドメインとから構成されるアダプターモジュールであって、前記ペプチドエピトープタグは、配列番号28または29によるヒト核タンパク質由来の短い線状エピトープである、アダプターモジュール。
- 前記アダブターモジュールの結合部位は、CD2、CD3、CD4、CD8、CD10、CD19、CD20、CD22、CD23、CD25、CD30、CD33、CD38、CD44、CD52、CD90、CD99、CD123、CD181、CD182、CD184、CD223、CD269(BCMA)、CD274、CD276、CD279およびCD366の表面抗原に結合する抗体または前記抗体のフラグメント、インターロイキン受容体、CXCR4、上皮成長因子受容体ファミリーのメンバー、腫瘍壊死因子受容体スーパーファミリーのメンバー、エフリン受容体、前立腺特異的抗原、前立腺幹細胞抗原(PSCA)および前立腺特異的膜抗原(PSMA)、胚性抗原、癌胚性抗原(CEA)および胎児アセチルコリン受容体、血管内皮増殖因子ファミリーのメンバー、上皮細胞接着分子EpCAM、アルファフェトプロテインAFP、ムチンタンパク質ファミリーのメンバー、卵胞刺激ホルモン受容体(FSHR)、ヒト高分子量メラノーマ関連抗原(HMW-MAA)、葉酸結合タンパク質FBP、α-葉酸受容体、NKG2D受容体のリガンド、サイトカイン受容体、上皮糖タンパク質ファミリーのメンバー、ジアシアロガングリオシド、炭酸脱水酵素ファミリーのメンバー、炭化水素抗原ファミリーのメンバー、Notchリガンド、メラノーマ関連コンドロイチン硫酸プロテオグリカン(MCSP)、糖タンパク質A33、および腫瘍特異的グリカン(上述のタンパク質およびタンパク質ファミリーの変異体を含む)、又はLa/SSB抗原のような細胞質抗原または核抗原、GTPaseのRhoファミリーのメンバー、高移動度タンパク質のメンバーなどに結合する抗体または前記抗体のフラグメントを含む、請求項8に記載のアダプターモジュール。
- 前記アダプターモジュールの前記結合部位は、T細胞受容体(TCR)または前記T細胞受容体のフラグメントのアルファ鎖およびベータ鎖またはガンマ鎖およびデルタ鎖から構成されており、TCR由来の結合部位は、ヒト白血球抗原クラス(HLA)IおよびIIタンパク質複合体により提示されるペプチドを認識しかつ前記ペプチドに結合し、EGFRファミリー、サバイビン、sry様高移動度box(SOX)タンパク質ファミリー、メラノーマ関連抗原および白血病関連抗原のようなタンパク質に由来するペプチドに特異的なTCRである、請求項8に記載のアダプターモジュール。
- 前記アダプターモジュールの前記結合部位は、タンパク質またはタンパク質複合体に対するリガンド(さらに受容体と言われる)またはそのフラグメントを有し、前記リガンドは、サイトカイン受容体、NKG2D受容体のリガンド、EGFRファミリーメンバーのリガンド、PD-1、CTLA-4、リンパ球活性化遺伝子3(LAG-3)またはT細胞免疫グロブリンおよびムチンドメイン含有3(TIM-3)のようなチェックポイント分子のリガンド、または自己反応性TCRに結合する、請求項8に記載のアダプターモジュール。
- 前記アダプターモジュールの結合部位は、化学反応(つまりクイックケミストリー)を介したタグ結合部位に融合される化学合成されたペプチド誘導体を有する、請求項8に記載のアダプターモジュール。
- アダプターモジュールの前記結合部位は、PSCAとPSMA、CD19とCD20、CD19とCD22、CD19とCD20とCD22、CD19とCD123、CD33とCD123、CD33とCD99、CD33とTIM-3、ErbB-1と-2、PSCAとErbB-2、IL-13Rα2とErbB-2、CD38とCD269とへの結合を含む二重および多重特異的抗原特異性を有する、請求項8から12までのいずれかに記載のアダプターモジュール。
- アダプターモジュールの前記タグ結合部位は、配列番号14および15または18および19によるLa/SSB抗原の5B9または7B6エピトープに結合する抗体または前記抗体のフラグメントを含む、請求項8から13までのいずれかに記載のアダプターモジュールをコードする核酸。
- アダプターモジュールの前記標的結合部位は、配列番号20および21または22および23によるPSMAまたはCD123に結合する抗体または前記抗体のフラグメントを含む、請求項8から13までのいずれかに記載のアダプターモジュールをコードする核酸。
- 請求項1から7までのいずれかに記載の核酸を有する細胞またはベクター。
- 前記細胞は、T細胞、ナチュラルキラー細胞、細胞障害性Tリンパ球、および制御性T細胞を含む免疫細胞の群から選択される、請求項16に記載の細胞。
- - 請求項16に記載のベクターと、
- 請求項8から13のいずれかに記載のアダプターモジュールおよび/または請求項14または15に記載の核酸をコードするベクターと
を有するキット。 - 被験者に投与するための、請求項16または17に記載の細胞および/または請求項8から13までのいずれかに記載のアダプターモジュールを有する調製物であって、前記細胞がRevCAR発現免疫細胞である、調製物。
- 哺乳類において逆ユニバーサルキメラ抗原レセプターにより媒介される免疫応答の刺激において使用するための、請求項16または17に記載の細胞および請求項8から13までのいずれかに記載のアダプターモジュール。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18177502.4A EP3581200A1 (en) | 2018-06-13 | 2018-06-13 | Reversed universal chimeric antigen receptor expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders |
EP18177502.4 | 2018-06-13 | ||
PCT/EP2019/065287 WO2019238722A1 (en) | 2018-06-13 | 2019-06-12 | Reversed universal chimeric antigen receptor expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021527404A JP2021527404A (ja) | 2021-10-14 |
JP7428663B2 true JP7428663B2 (ja) | 2024-02-06 |
Family
ID=62783995
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020569080A Active JP7428663B2 (ja) | 2018-06-13 | 2019-06-12 | いくつかの多重抗原の標的用の逆ユニバーサルキメラ抗原受容体を発現する免疫細胞ならびにその製造方法ならびに癌、感染症および自己免疫疾患を治療するためのその使用 |
Country Status (9)
Country | Link |
---|---|
US (1) | US20210309751A1 (ja) |
EP (2) | EP3581200A1 (ja) |
JP (1) | JP7428663B2 (ja) |
KR (1) | KR20210021347A (ja) |
CN (1) | CN112218653A (ja) |
AU (1) | AU2019286554A1 (ja) |
CA (1) | CA3100566A1 (ja) |
IL (1) | IL279146A (ja) |
WO (1) | WO2019238722A1 (ja) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110358734B (zh) * | 2019-06-13 | 2020-08-25 | 首都医科大学宣武医院 | 以Tcm为主要效应成分的CAR-T制备方法及其应用 |
AU2021396403A1 (en) | 2020-12-11 | 2023-06-29 | Intellia Therapeutics, Inc. | Compositions and methods for reducing mhc class ii in a cell |
US11883432B2 (en) | 2020-12-18 | 2024-01-30 | Century Therapeutics, Inc. | Chimeric antigen receptor system with adaptable receptor specificity |
CR20230320A (es) | 2020-12-23 | 2023-10-23 | Intellia Therapeutics Inc | Composiciones y métodos para reducir los hla-a en una célula |
WO2022140587A1 (en) | 2020-12-23 | 2022-06-30 | Intellia Therapeutics, Inc. | Compositions and methods for genetically modifying ciita in a cell |
JP2024502036A (ja) | 2020-12-30 | 2024-01-17 | インテリア セラピューティクス,インコーポレイテッド | 操作されたt細胞 |
WO2022170172A1 (en) | 2021-02-08 | 2022-08-11 | Intellia Therapeutics, Inc. | Natural killer cell receptor 2b4 compositions and methods for immunotherapy |
EP4288089A2 (en) | 2021-02-08 | 2023-12-13 | Intellia Therapeutics, Inc. | T-cell immunoglobulin and mucin domain 3 (tim3) compositions and methods for immunotherapy |
EP4288088A2 (en) | 2021-02-08 | 2023-12-13 | Intellia Therapeutics, Inc. | Lymphocyte activation gene 3 (lag3) compositions and methods for immunotherapy |
KR20220159507A (ko) * | 2021-05-25 | 2022-12-05 | 한국생명공학연구원 | ErbB3 특이적인 키메라 항원 수용체 및 이를 발현하는 면역세포 치료제 |
WO2023028471A1 (en) | 2021-08-24 | 2023-03-02 | Intellia Therapeutics, Inc. | Programmed cell death protein 1 (pd1) compositions and methods for cell-based therapy |
WO2023081200A2 (en) | 2021-11-03 | 2023-05-11 | Intellia Therapeutics, Inc. | Cd38 compositions and methods for immunotherapy |
WO2023245108A2 (en) | 2022-06-16 | 2023-12-21 | Intellia Therapeutics, Inc. | Compositions and methods for reducing mhc class i in a cell |
WO2023250489A1 (en) | 2022-06-23 | 2023-12-28 | Avencell Therapeutics Inc. | Targeting modules against cd123 for use in a method for stimulating a chimeric antigen receptor-mediated immune response in a mammal |
WO2023247727A2 (en) | 2022-06-23 | 2023-12-28 | Ehninger Dr Armin | Engineered human t cells comprising a switchable chimeric antigen cell surface receptor and methods for generating them |
EP4295860A1 (en) | 2022-06-23 | 2023-12-27 | Armin Ehninger | Engineered human t cells comprising a switchable chimeric antigen cell surface receptor and methods for generating them |
EP4296281A1 (en) | 2022-06-23 | 2023-12-27 | AvenCell Therapeutics Inc. | Targeting modules against cd123 and a tag for use in a method for stimulating a universal chimeric antigen receptor-mediated immune response in a mammal |
WO2024006955A1 (en) | 2022-06-29 | 2024-01-04 | Intellia Therapeutics, Inc. | Engineered t cells |
EP4342907A1 (en) | 2022-09-21 | 2024-03-27 | AvenCell Europe GmbH | Switchable chimeric antigen receptors and their use |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180118808A1 (en) | 2015-03-26 | 2018-05-03 | The California Institute For Biomedical Research | SWITCHABLE NON-scFv CHIMERIC RECEPTORS, SWITCHES, AND USES THEREOF |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101037475B (zh) * | 2006-03-15 | 2012-08-15 | 上海中信国健药业股份有限公司 | 一种嵌合受体及其制备方法和用途 |
WO2012082841A2 (en) | 2010-12-14 | 2012-06-21 | University Of Maryland, Baltimore | Universal anti-tag chimeric antigen receptor-expressing t cells and methods of treating cancer |
WO2013044225A1 (en) | 2011-09-22 | 2013-03-28 | The Trustees Of The University Of Pennsylvania | A universal immune receptor expressed by t cells for the targeting of diverse and multiple antigens |
ES2688035T3 (es) | 2014-08-29 | 2018-10-30 | Gemoab Monoclonals Gmbh | Receptor de antígeno universal que expresa células inmunes para direccionamiento de antígenos múltiples diversos, procedimiento para fabricación del mismo y utilización del mismo para tratamiento de cáncer, infecciones y enfermedades autoinmunes |
WO2017112784A1 (en) * | 2015-12-22 | 2017-06-29 | The Trustees Of The University Of Pennsylvania | Spycatcher and spytag: universal immune receptors for t cells |
-
2018
- 2018-06-13 EP EP18177502.4A patent/EP3581200A1/en active Pending
-
2019
- 2019-06-12 CN CN201980037303.1A patent/CN112218653A/zh active Pending
- 2019-06-12 EP EP19729046.3A patent/EP3806892A1/en active Pending
- 2019-06-12 KR KR1020217000272A patent/KR20210021347A/ko active Search and Examination
- 2019-06-12 CA CA3100566A patent/CA3100566A1/en active Pending
- 2019-06-12 US US17/251,447 patent/US20210309751A1/en active Pending
- 2019-06-12 AU AU2019286554A patent/AU2019286554A1/en active Pending
- 2019-06-12 JP JP2020569080A patent/JP7428663B2/ja active Active
- 2019-06-12 WO PCT/EP2019/065287 patent/WO2019238722A1/en unknown
-
2020
- 2020-12-01 IL IL279146A patent/IL279146A/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180118808A1 (en) | 2015-03-26 | 2018-05-03 | The California Institute For Biomedical Research | SWITCHABLE NON-scFv CHIMERIC RECEPTORS, SWITCHES, AND USES THEREOF |
Non-Patent Citations (1)
Title |
---|
Blood,2019年11月13日,Vol.134 supplement 1,ArticleNo.5611 |
Also Published As
Publication number | Publication date |
---|---|
JP2021527404A (ja) | 2021-10-14 |
WO2019238722A1 (en) | 2019-12-19 |
AU2019286554A1 (en) | 2021-01-28 |
EP3806892A1 (en) | 2021-04-21 |
US20210309751A1 (en) | 2021-10-07 |
CN112218653A (zh) | 2021-01-12 |
IL279146A (en) | 2021-01-31 |
CA3100566A1 (en) | 2019-12-19 |
EP3581200A1 (en) | 2019-12-18 |
KR20210021347A (ko) | 2021-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7428663B2 (ja) | いくつかの多重抗原の標的用の逆ユニバーサルキメラ抗原受容体を発現する免疫細胞ならびにその製造方法ならびに癌、感染症および自己免疫疾患を治療するためのその使用 | |
US10766943B2 (en) | Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders | |
US20210137977A1 (en) | Diverse antigen binding domains, novel platforms and other enhancements for cellular therapy | |
US20190048085A1 (en) | Modified cells for immunotherapy | |
JP2019088330A (ja) | 二重特異性キメラ抗原受容体およびその治療的使用 | |
JP2023110028A (ja) | 共通キメラ抗原受容体発現免疫細胞のためのターゲティングモジュールならびに癌、感染および自己免疫障害の処置における使用 | |
JP7271037B2 (ja) | 免疫シナプスを安定化させるキメラ抗原受容体(car)t細胞 | |
CA3136618A1 (en) | Flt3-specific chimeric antigen receptors and methods of using the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220517 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230530 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230830 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231025 |
|
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: 20240104 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240125 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7428663 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |