DK2970482T3 - Behandling af cancer under anvendelse af humaniseret kimær anti-cd19-antigenreceptor - Google Patents
Behandling af cancer under anvendelse af humaniseret kimær anti-cd19-antigenreceptor Download PDFInfo
- Publication number
- DK2970482T3 DK2970482T3 DK14722469.5T DK14722469T DK2970482T3 DK 2970482 T3 DK2970482 T3 DK 2970482T3 DK 14722469 T DK14722469 T DK 14722469T DK 2970482 T3 DK2970482 T3 DK 2970482T3
- Authority
- DK
- Denmark
- Prior art keywords
- seq
- sequence
- cell
- car
- domain
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 134
- 201000011510 cancer Diseases 0.000 title claims description 73
- 238000011282 treatment Methods 0.000 title claims description 54
- 239000000126 substance Substances 0.000 title description 5
- 102000006306 Antigen Receptors Human genes 0.000 title description 4
- 108010083359 Antigen Receptors Proteins 0.000 title description 4
- 210000004027 cell Anatomy 0.000 claims description 443
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 400
- 230000027455 binding Effects 0.000 claims description 244
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 196
- 150000007523 nucleic acids Chemical class 0.000 claims description 177
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 136
- 230000004068 intracellular signaling Effects 0.000 claims description 135
- 238000000034 method Methods 0.000 claims description 118
- 239000013598 vector Substances 0.000 claims description 118
- 230000011664 signaling Effects 0.000 claims description 110
- 108090000623 proteins and genes Proteins 0.000 claims description 108
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 106
- 102000039446 nucleic acids Human genes 0.000 claims description 101
- 108020004707 nucleic acids Proteins 0.000 claims description 101
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 94
- 229920001184 polypeptide Polymers 0.000 claims description 90
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 89
- 230000014509 gene expression Effects 0.000 claims description 87
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 74
- 102000004169 proteins and genes Human genes 0.000 claims description 71
- 241000282414 Homo sapiens Species 0.000 claims description 70
- 230000004048 modification Effects 0.000 claims description 67
- 238000012986 modification Methods 0.000 claims description 67
- 239000003795 chemical substances by application Substances 0.000 claims description 66
- 201000010099 disease Diseases 0.000 claims description 61
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 60
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 59
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 53
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 53
- 108020004414 DNA Proteins 0.000 claims description 50
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 37
- 230000002401 inhibitory effect Effects 0.000 claims description 36
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 34
- 238000000338 in vitro Methods 0.000 claims description 34
- 230000004936 stimulating effect Effects 0.000 claims description 34
- 230000000694 effects Effects 0.000 claims description 29
- 102100027207 CD27 antigen Human genes 0.000 claims description 24
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 24
- 108091008874 T cell receptors Proteins 0.000 claims description 23
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 23
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims description 22
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 22
- 241000124008 Mammalia Species 0.000 claims description 20
- 230000036210 malignancy Effects 0.000 claims description 20
- -1 CD86 Proteins 0.000 claims description 19
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 19
- 230000002489 hematologic effect Effects 0.000 claims description 19
- 208000032839 leukemia Diseases 0.000 claims description 19
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims description 18
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 18
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 18
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 18
- 108020005345 3' Untranslated Regions Proteins 0.000 claims description 17
- 239000013612 plasmid Substances 0.000 claims description 16
- 241000713666 Lentivirus Species 0.000 claims description 14
- 201000003444 follicular lymphoma Diseases 0.000 claims description 14
- 201000005787 hematologic cancer Diseases 0.000 claims description 14
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 13
- 230000002062 proliferating effect Effects 0.000 claims description 13
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 12
- 208000006994 Precancerous Conditions Diseases 0.000 claims description 12
- 208000007541 Preleukemia Diseases 0.000 claims description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 11
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 11
- 108091036407 Polyadenylation Proteins 0.000 claims description 11
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 10
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 10
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 10
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 210000000601 blood cell Anatomy 0.000 claims description 9
- 208000024207 chronic leukemia Diseases 0.000 claims description 9
- 230000003211 malignant effect Effects 0.000 claims description 9
- 230000001177 retroviral effect Effects 0.000 claims description 9
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 8
- 206010058314 Dysplasia Diseases 0.000 claims description 8
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 8
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 8
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 8
- 102100025390 Integrin beta-2 Human genes 0.000 claims description 8
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 8
- 230000000735 allogeneic effect Effects 0.000 claims description 8
- 230000001589 lymphoproliferative effect Effects 0.000 claims description 8
- 208000007525 plasmablastic lymphoma Diseases 0.000 claims description 8
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 claims description 7
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 7
- 102100037904 CD9 antigen Human genes 0.000 claims description 7
- 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 claims description 7
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 7
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 claims description 7
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims description 7
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 claims description 7
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims description 7
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 7
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 7
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 claims description 7
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 7
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 7
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 claims description 7
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims description 7
- 206010025323 Lymphomas Diseases 0.000 claims description 7
- 201000003791 MALT lymphoma Diseases 0.000 claims description 7
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 7
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 7
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 7
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 claims description 7
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 7
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 7
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims description 7
- 208000021937 marginal zone lymphoma Diseases 0.000 claims description 7
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 241000701161 unidentified adenovirus Species 0.000 claims description 6
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 5
- 230000005809 anti-tumor immunity Effects 0.000 claims description 4
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
- 230000002463 transducing effect Effects 0.000 claims description 3
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 208000004736 B-Cell Leukemia Diseases 0.000 claims 1
- 208000003950 B-cell lymphoma Diseases 0.000 claims 1
- 208000000389 T-cell leukemia Diseases 0.000 claims 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims 1
- 210000002768 hair cell Anatomy 0.000 claims 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 claims 1
- 230000001926 lymphatic effect Effects 0.000 claims 1
- 239000000427 antigen Substances 0.000 description 103
- 108091007433 antigens Proteins 0.000 description 103
- 102000036639 antigens Human genes 0.000 description 103
- 230000000139 costimulatory effect Effects 0.000 description 80
- 238000006467 substitution reaction Methods 0.000 description 71
- 235000018102 proteins Nutrition 0.000 description 69
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 58
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 58
- 102000053602 DNA Human genes 0.000 description 49
- 230000000295 complement effect Effects 0.000 description 48
- 239000000203 mixture Substances 0.000 description 48
- 125000003729 nucleotide group Chemical group 0.000 description 48
- 229920002477 rna polymer Polymers 0.000 description 48
- 239000011324 bead Substances 0.000 description 43
- 235000001014 amino acid Nutrition 0.000 description 42
- 229940024606 amino acid Drugs 0.000 description 38
- 150000001413 amino acids Chemical class 0.000 description 38
- 108020004999 messenger RNA Proteins 0.000 description 37
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 35
- 102100035932 Cocaine- and amphetamine-regulated transcript protein Human genes 0.000 description 34
- 101000715592 Homo sapiens Cocaine- and amphetamine-regulated transcript protein Proteins 0.000 description 34
- 239000002773 nucleotide Substances 0.000 description 34
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 33
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 33
- 239000002245 particle Substances 0.000 description 28
- 239000012634 fragment Substances 0.000 description 25
- 150000002632 lipids Chemical class 0.000 description 25
- 238000013518 transcription Methods 0.000 description 25
- 230000035897 transcription Effects 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 21
- 238000003752 polymerase chain reaction Methods 0.000 description 20
- 125000000539 amino acid group Chemical group 0.000 description 19
- 230000001086 cytosolic effect Effects 0.000 description 19
- 230000000638 stimulation Effects 0.000 description 19
- 108060003951 Immunoglobulin Proteins 0.000 description 18
- 230000004913 activation Effects 0.000 description 18
- 102000018358 immunoglobulin Human genes 0.000 description 18
- 102000040430 polynucleotide Human genes 0.000 description 18
- 108091033319 polynucleotide Proteins 0.000 description 18
- 239000002157 polynucleotide Substances 0.000 description 18
- 230000006870 function Effects 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 241001529936 Murinae Species 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 108020003589 5' Untranslated Regions Proteins 0.000 description 15
- 239000003446 ligand Substances 0.000 description 15
- 239000002502 liposome Substances 0.000 description 15
- 239000000523 sample Substances 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 238000013519 translation Methods 0.000 description 14
- 210000004881 tumor cell Anatomy 0.000 description 14
- 108010005327 CD19-specific chimeric antigen receptor Proteins 0.000 description 13
- 102100025278 Coxsackievirus and adenovirus receptor Human genes 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- 230000028993 immune response Effects 0.000 description 13
- 230000003834 intracellular effect Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 230000010261 cell growth Effects 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 241000283984 Rodentia Species 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000002983 circular dichroism Methods 0.000 description 11
- 230000007423 decrease Effects 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 11
- 210000004602 germ cell Anatomy 0.000 description 11
- 230000001976 improved effect Effects 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 108020004705 Codon Proteins 0.000 description 10
- 101100383038 Homo sapiens CD19 gene Proteins 0.000 description 10
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 9
- 102100024263 CD160 antigen Human genes 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 9
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 9
- 208000034578 Multiple myelomas Diseases 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000012636 effector Substances 0.000 description 9
- 238000004611 spectroscopical analysis Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 206010000830 Acute leukaemia Diseases 0.000 description 8
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 8
- 108010024755 CTL019 chimeric antigen receptor Proteins 0.000 description 8
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 8
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 8
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 8
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 8
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 108700008625 Reporter Genes Proteins 0.000 description 8
- 238000002617 apheresis Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 238000009126 molecular therapy Methods 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 125000006850 spacer group Chemical group 0.000 description 8
- 239000013603 viral vector Substances 0.000 description 8
- 108010074708 B7-H1 Antigen Proteins 0.000 description 7
- 241000282693 Cercopithecidae Species 0.000 description 7
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 7
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 7
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 7
- 102000017578 LAG3 Human genes 0.000 description 7
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 7
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 7
- 108700019146 Transgenes Proteins 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 230000000977 initiatory effect Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 229940090044 injection Drugs 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 241000894007 species Species 0.000 description 7
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 7
- 241001430294 unidentified retrovirus Species 0.000 description 7
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 6
- 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 6
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 6
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 6
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 6
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 6
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 6
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 6
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000002659 cell therapy Methods 0.000 description 6
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 239000005090 green fluorescent protein Substances 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 201000009277 hairy cell leukemia Diseases 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 210000005259 peripheral blood Anatomy 0.000 description 6
- 239000011886 peripheral blood Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 230000019491 signal transduction Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 239000004474 valine Substances 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 5
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 5
- 108700026244 Open Reading Frames Proteins 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 238000004520 electroporation Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 5
- 238000001476 gene delivery Methods 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 229940121354 immunomodulator Drugs 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- 230000008488 polyadenylation Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 108091033380 Coding strand Proteins 0.000 description 4
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 4
- 229930105110 Cyclosporin A Natural products 0.000 description 4
- 108010036949 Cyclosporine Proteins 0.000 description 4
- 241000702421 Dependoparvovirus Species 0.000 description 4
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 4
- 102000050627 Glucocorticoid-Induced TNFR-Related Human genes 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 4
- 108091034057 RNA (poly(A)) Proteins 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 229960001265 ciclosporin Drugs 0.000 description 4
- 229930182912 cyclosporin Natural products 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000003463 hyperproliferative effect Effects 0.000 description 4
- 239000012642 immune effector Substances 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- 229960004942 lenalidomide Drugs 0.000 description 4
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 230000005291 magnetic effect Effects 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- 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 4
- 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 4
- 229920000642 polymer Polymers 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 3
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 3
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 3
- 108090000331 Firefly luciferases Proteins 0.000 description 3
- 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 3
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 239000000232 Lipid Bilayer Substances 0.000 description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 230000006052 T cell proliferation Effects 0.000 description 3
- 101710187882 Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 3
- 108091023045 Untranslated Region Proteins 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000001461 cytolytic effect Effects 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 229960000390 fludarabine Drugs 0.000 description 3
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 230000008676 import Effects 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- FVVLHONNBARESJ-NTOWJWGLSA-H magnesium;potassium;trisodium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;acetate;tetrachloride;nonahydrate Chemical compound O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Mg+2].[Cl-].[Cl-].[Cl-].[Cl-].[K+].CC([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O FVVLHONNBARESJ-NTOWJWGLSA-H 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 230000002688 persistence Effects 0.000 description 3
- 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 102220080600 rs797046116 Human genes 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000001542 size-exclusion chromatography Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 238000011476 stem cell transplantation Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102100038078 CD276 antigen Human genes 0.000 description 2
- 101710185679 CD276 antigen Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 102100035793 CD83 antigen Human genes 0.000 description 2
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 2
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 2
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102100039064 Interleukin-3 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 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
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 101710124239 Poly(A) polymerase Proteins 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 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
- 102100037116 Transcription elongation factor 1 homolog Human genes 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 150000003838 adenosines Chemical class 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 238000010256 biochemical assay Methods 0.000 description 2
- 238000002306 biochemical method Methods 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229940112129 campath Drugs 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229940119744 dextran 40 Drugs 0.000 description 2
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 238000001325 log-rank test Methods 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000004324 lymphatic system Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 108091005763 multidomain proteins Proteins 0.000 description 2
- 229940014456 mycophenolate Drugs 0.000 description 2
- 229960000951 mycophenolic acid Drugs 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 229960003452 romidepsin Drugs 0.000 description 2
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 150000003431 steroids Chemical class 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
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- 230000010512 thermal transition Effects 0.000 description 2
- 101150095421 tig gene Proteins 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 108010065816 zeta chain antigen T cell receptor Proteins 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- 108010082808 4-1BB Ligand Proteins 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 108020005176 AU Rich Elements Proteins 0.000 description 1
- PITHJRRCEANNKJ-UHFFFAOYSA-N Aclacinomycin A Natural products C12=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C=C2C(C(=O)OC)C(CC)(O)CC1OC(OC1C)CC(N(C)C)C1OC(OC1C)CC(O)C1OC1CCC(=O)C(C)O1 PITHJRRCEANNKJ-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 241000714230 Avian leukemia virus Species 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 208000035143 Bacterial infection 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
- 108010087504 Beta-Globulins Proteins 0.000 description 1
- 102000006734 Beta-Globulins Human genes 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 108091033409 CRISPR Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 101100510617 Caenorhabditis elegans sel-8 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000701867 Enterobacteria phage T7 Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 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
- 241000282326 Felis catus Species 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102100027377 HBS1-like protein Human genes 0.000 description 1
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101100005238 Homo sapiens CARTPT gene Proteins 0.000 description 1
- 101001009070 Homo sapiens HBS1-like protein Proteins 0.000 description 1
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000971538 Homo sapiens Killer cell lectin-like receptor subfamily F member 1 Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 1
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 description 1
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 101150102264 IE gene Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102100021458 Killer cell lectin-like receptor subfamily F member 1 Human genes 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- 108091008877 NK cell receptors Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007019 Oxalis corniculata Species 0.000 description 1
- 208000030852 Parasitic disease Diseases 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
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin 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
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 102000015623 Polynucleotide Adenylyltransferase Human genes 0.000 description 1
- 108010024055 Polynucleotide adenylyltransferase Proteins 0.000 description 1
- 102100037935 Polyubiquitin-C Human genes 0.000 description 1
- 208000008691 Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 108010065868 RNA polymerase SP6 Proteins 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 102100029198 SLAM family member 7 Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010062314 Signaling Lymphocytic Activation Molecule Family Proteins 0.000 description 1
- 102000010841 Signaling Lymphocytic Activation Molecule Family Human genes 0.000 description 1
- 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 description 1
- 102000008115 Signaling Lymphocytic Activation Molecule Family Member 1 Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
- 108010056354 Ubiquitin C Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
- 229960004176 aclarubicin Drugs 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002487 adenosine deaminase inhibitor Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- FIVPIPIDMRVLAY-UHFFFAOYSA-N aspergillin Natural products C1C2=CC=CC(O)C2N2C1(SS1)C(=O)N(C)C1(CO)C2=O FIVPIPIDMRVLAY-UHFFFAOYSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 108010028263 bacteriophage T3 RNA polymerase Proteins 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 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
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 229940108502 bicnu Drugs 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- 229960004395 bleomycin sulfate Drugs 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960005520 bryostatin Drugs 0.000 description 1
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 229940111214 busulfan injection Drugs 0.000 description 1
- 229940112133 busulfex Drugs 0.000 description 1
- 230000000981 bystander Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000003710 calcium ionophore Substances 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 208000018805 childhood acute lymphoblastic leukemia Diseases 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000000978 circular dichroism spectroscopy Methods 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 108700032673 cocaine- and amphetamine-regulated transcript Proteins 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 239000013632 covalent dimer Substances 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229940077926 cytarabine liposome injection Drugs 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 229940070968 depocyt Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940093541 dicetylphosphate Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000002022 differential scanning fluorescence spectroscopy Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 229960000284 efalizumab Drugs 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000004993 emission spectroscopy Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- 238000012239 gene modification 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
- FIVPIPIDMRVLAY-RBJBARPLSA-N gliotoxin Chemical compound C1C2=CC=C[C@H](O)[C@H]2N2[C@]1(SS1)C(=O)N(C)[C@@]1(CO)C2=O FIVPIPIDMRVLAY-RBJBARPLSA-N 0.000 description 1
- 229940103893 gliotoxin Drugs 0.000 description 1
- 229930190252 gliotoxin Natural products 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 108010033706 glycylserine Proteins 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 229940064366 hespan Drugs 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000008004 immune attack Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940063725 leukeran Drugs 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 229940090009 myleran Drugs 0.000 description 1
- POFWRMVFWIJXHP-UHFFFAOYSA-N n-benzyl-9-(oxan-2-yl)purin-6-amine Chemical compound C=1C=CC=CC=1CNC(C=1N=C2)=NC=NC=1N2C1CCCCO1 POFWRMVFWIJXHP-UHFFFAOYSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 108010069768 negative elongation factor Proteins 0.000 description 1
- 230000011234 negative regulation of signal transduction Effects 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 108010058237 plasma protein fraction Proteins 0.000 description 1
- 229940081858 plasmalyte a Drugs 0.000 description 1
- 229940002993 plasmanate Drugs 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 102220058139 rs372082751 Human genes 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 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
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 108010078373 tisagenlecleucel Proteins 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/3061—Blood 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
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464411—Immunoglobulin superfamily
- A61K39/464412—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- 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
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- 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
- 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
- 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
-
- 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
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
-
- 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
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/48—Blood cells, e.g. leukemia or lymphoma
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2510/02—Cells for production
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Claims (17)
1. Humaniseret anti-CD 19-bindingsdomæne, hvor det humaniserede anti-CD 19-bindingsdomæne omfatter en aminosyresekvens af et scFv udvalgt blandt SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11 eller SEQ ID NO:12.
2. Isoleret nukleinsyremolekyle, der koder for en kimær antigenreceptor (CAR), hvor CAR'en omfatter et antistof eller antistoffragment, som indbefatter et humaniseret anti-CD 19-bindingsdomæne ifølge krav 1, et transmembrandomæne og et intracellulært signaleringsdomæne omfattende et stimulerende domæne.
3. Isoleret nukleinsyremolekyle ifølge krav 2, omfattende: (i) en nukleinsyresekvens af et humaniseret anti-CD 19-bindingsdomæne ifølge et hvilket som helst af SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71 og SEQ ID NO:72 eller en sekvens med 95-99 % identitet dermed; (ii) nukleinsyre, der koder for en CAR-aminosyresekvens med SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO: 33, SEQ ID NO:34, SEQ ID NO: 35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41 eller SEQ ID NO:42 eller en aminosyresekvens med 85 %, 90 %, 95 %, 96 %, 97 %, 98 % eller 99 % identitet dermed; og/eller (iii) en nukleinsyresekvens af SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95 eller SEQ ID NO:96 eller en nukleinsyresekvens med mindst 95 % identitet dermed.
4. Isoleret nukleinsyremolekyle ifølge krav 2 eller 3, hvor: (i) den kodede CAR indbefatter et transmembrandomæne, der omfatter et transmembrandomæne af et protein udvalgt fra gruppen bestående af alfa-, beta- eller zeta-kæden af T-celle-receptoren, CD28, CD3-epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 og CD154; (ii) det kodede transmembrandomæne omfatter en sekvens med SEQ ID NO: 15; (iii) det kodede transmembrandomæne omfatter en aminosyresekvens, der omfatter mindst en, to eller tre modifikationer, men ikke mere end 20, 10 eller 5 modifikationer af en aminosyresekvens med SEQ ID NO:15 eller en sekvens med 95-99 % identitet med en aminosyresekvens med SEQ ID NO:15; (iv) nukleinsyresekvensen, der koder for transmembrandomænet, omfatter en sekvens med SEQ ID NO:56 eller en sekvens med 95-99 % identitet dermed; og/eller (v) det kodede anti-CD 19-bindingsdomæne er forbundet med transmembrandomænet med en hængselregion, eventuelt hvor enten: (a) den kodede hængselregion omfatter SEQ ID NO:14 eller SEQ ID NO:102 eller en sekvens med 95-99 % identitet dermed; eller (b) nukleinsyresekvensen, der koder for hængselregionen, omfatter en sekvens med SEQ ID NO: 55 eller en sekvens med 95-99 % identitet dermed.
5. Isoleret nukleinsyremolekyle ifølge et hvilket som helst af kravene 2 til 4, yderligere omfattende en sekvens, der koder for et co-stimulerende domæne, f.eks. et co-stimulerende domæne, der er et funktionelt signaleringsdomæne opnået fra et protein udvalgt fra gruppen bestående af 0X40, CD2, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278) og 4-1BB (CD137), eventuelt hvor: (i) det kodede co-stimulerende domæne omfatter en sekvens med SEQ ID NO:16; (ii) det kodede co-stimulerende domæne omfatter en aminosyresekvens med mindst en, to eller tre modifikationer, men ikke mere end 20,10 eller 5 modifikationer af en aminosyresekvens med SEQ ID NO:16 eller en sekvens med 95-99 % identitet med en aminosyresekvens med SEQ ID NO:16; eller (iii) nukleinsyresekvensen, der koder for det co-stimulerende domæne, omfatter en sekvens med SEQ ID NO:60 eller en sekvens med 95-99 % identitet dermed.
6. Isoleret nukleinsyremolekyle ifølge et hvilket som helst af kravene 2 til 5, hvor: (i) det kodede intracellulære signaleringsdomæne omfatter et funktionelt signaleringsdomæne af 4-1BB og/eller et funktionelt signaleringsdomæne af CD3 zeta; (ii) det kodede intracellulære signaleringsdomæne omfatter sekvensen med SEQ ID NO: 16 og/eller sekvensen med SEQ ID NO:17 eller SEQ ID NO:43; (iii) det intracellulære signaleringsdomæne omfatter en aminosyresekvens med mindst en, to eller tre modifikationer, men ikke mere end 20, 10 eller 5 modifikationer af en aminosyresekvens med SEQ ID NO:16 og/eller en aminosyresekvens med SEQ ID NO:17 eller SEQ ID NO:43 eller en sekvens med 95-99 % identitet med en aminosyresekvens med SEQ ID NO:16 og/eller en aminosyresekvens med SEQ ID NO:17 eller SEQ ID NO:43; (iv) det kodede intracellulære signaleringsdomæne omfatter sekvensen med SEQ ID NO:16 og sekvensen med SEQ ID NO:17 eller SEQ ID NO:43, hvor sekvenserne, der omfatter det intracellulære signaleringsdomæne, eksprime-res i den samme ramme og som en enkelt polypeptidkæde; (v) nukleinsyresekvensen, der koder for det intracellulære signaleringsdomæne, omfatter en sekvens med SEQ ID NO:60 eller en sekvens med 95-99 % identitet dermed og/eller en sekvens med SEQ ID NO:101 eller SEQ ID NO:44 eller en sekvens med 95-99 % identitet; og/eller (vi) det isolerede nukleinsyremolekyle endvidere koder for en leader-sekvens, eventuelt hvor leader-sekvensen omfatter SEQ ID NO: 13 eller en sekvens med 95-99 % identitet med en aminosyresekvens med SEQ ID NO:13.
7. Isoleret polypeptidmolekyle, der kodes af nukleinsyremolekylet ifølge et hvilket som helst af kravene 2-6.
8. Isoleret kimær antigenreceptor (CAR)-molekyle omfattende et humaniseret anti-CD19-bindingsdomæne ifølge krav 1, et transmembrandomæne og et int-racellulært signaleringsdomæne.
9. Isoleret CAR-molekyle ifølge krav 8, hvor: (i) CAR'en er en CAR ifølge et hvilket som helst af kravene 2-7; eller (ii) CAR'en omfatter en sekvens udvalgt fra gruppen bestående af SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID N0:41, and SEQ ID NO:42 eller en sekvens med 95-99 % identitet dermed.
10. Vektor omfattende et nukleinsyremolekyle, der koder for en CAR ifølge et hvilket som helst af de foregående krav, eventuelt hvor: (i) vektoren er udvalgt fra gruppen bestående af en DNA, en RNA, et plasmid, en lentivirusvektor, adenovirusvektor eller en retrovirusvektor; (ii) vektoren endvidere omfatter en promoter, f.eks. en EF-1-promoter eller en EF-1-promoter, der omfatter en sekvens med SEQ ID NO: 100; (iii) vektoren er en in vitro-transskriberet vektor; (iv) nukleinsyresekvensen i vektoren endvidere omfatter en poly (A)-hale; og/eller (v) nukleinsyresekvensen i vektoren endvidere omfatter en 3'UTR.
11. Celle omfattende vektoren ifølge krav 10, eventuelt hvor cellen er en human T-celle, f.eks. en CD8+ T-celle.
12. Fremgangsmåde til at: (i) fremstille en celle, omfattende at transducere en T-celle med en vektor ifølge krav 10; eller (ii) frembringe en population af RNA-manipulerede celler, omfattende at indføre en in vitro-transskriberet RNA eller syntetisk RNA i en celle, hvor RNA'en omfatter en nukleinsyre, der koder for et CAR-molekyle ifølge et hvilket som helst af de foregående krav.
13. Celle, der eksprimerer et CAR-molekyle, hvor CAR-molekylet er et CAR-molekyle som defineret i et hvilket som helst af de foregående krav, til anvendelse i: (a) en fremgangsmåde til tilvejebringelse afen antitumorimmunitet hos et pattedyr, hvilken fremgangsmåde omfatter at indgive en virksom mængde af cellen, der eksprimerer CAR-molekylet, til pattedyret, eventuelt hvor: (i) cellen er en autolog T-celle; (ii) cellen er en allogen T-celle; og/eller (iii) cellen indgives til et menneske; eller (b) en fremgangsmåde til behandling af et pattedyr, som har en sygdom, der er forbundet med ekspression af CD19, hvilken fremgangsmåde omfatter at indgive en virksom mængde af cellen til pattedyret.
14. Celle til anvendelse ifølge krav 13(b), hvor: (i) sygdommen, der er forbundet med CD19-ekspression, er udvalgt blandt en proliferativ sygdom, såsom en cancer eller malignitet eller en præcancerøs tilstand, såsom en myelodysplasi, et myelodysplastisk syndrom eller en præleukæmi, eller er en ikke-cancerrelateret indikation, der er forbundet med ekspression af CD19; (ii) sygdommen er en hæmatologisk cancer udvalgt fra gruppen bestående af en eller flere leukæmier, herunder, men ikke begrænset til, akut lymfatisk B-celle-leukæmi ("BALL"), akut lymfatisk T-celle-leukæmi ("TALL"), akut lymfatisk leukæmi (ALL); en eller flere kroniske leukæmier, herunder, men ikke begrænset til, kronisk myelogen leukæmi (CML), kronisk lymfatisk leukæmi (CLL); og yderligere hæmatologiske cancere eller hæmatologiske tilstande, herunder, men ikke begrænset til, B-celle-prolymfocyt-leukæmi, biastisk plas-macytoid dendritisk celle-neoplasma, Burkitts lymfom, diffust storcellet B-celle-lymfom, follikulært lymfom, hårcelleleukæmi, småcellet eller storcellet-folliku-lært lymfom, maligne lymfoproliferative tilstande, MALT-lymfom, kappecel-lelymfom, marginalzonelymfom, myelomatose, myelodysplasi og myelodysplastisk syndrom, non-Hodgkins lymfom, plasmablastisk lymfom, plas-macytoid dendritisk celle-neoplasma, Waldenstrom macroglobulinæmi og "præleukæmi", som er en forskelligartet samling af hæmatologiske tilstande, der har ineffektiv produktion (eller dysplasi) af myeloide blodceller; og sygdommen, der er forbundet med CD19-ekspression indbefatter, men ikke er begrænset til, atypiske og/eller ikke-klassiske cancere, maligniteter, præcancerøse tilstande eller proliferative sygdomme, der eksprimerer CD19; og kombinationer deraf; (iii) cellerne, der eksprimerer et CAR-molekyle, indgives i kombination med et middel, der øger effekten af en celle, der eksprimerer et CAR-molekyle; (iv) cellerne, der eksprimerer et CAR-molekyle, indgives i kombination med et middel, der forbedrer en eller flere bivirkninger forbundet med indgivelse af en celle, der eksprimerer et CAR-molekyle; og/eller (v) cellerne, der eksprimerer et CAR-molekyle, indgives i kombination med et middel, der behandler sygdommen, der er forbundet med CD19-ekspression.
15. Anti-CD 19-bindingsdomæne ifølge krav 1, isoleret nukleinsyremolekyle ifølge et hvilket som helst af kravene 2-6, isoleret polypeptidmolekyle ifølge krav 7, isoleret CAR-molekyle ifølge krav 8 eller 9, vektor ifølge krav 10 eller celle ifølge krav 11 til anvendelse ved behandling af en sygdom, der er forbundet med CD19-ekspression, eller til anvendelse ved behandling af cancer, f.eks. en hæmatologisk cancer.
16. Anti-CD 19-bindingsdomæne ifølge krav 1, hvor det isoleret nukleinsyremolekyle ifølge et hvilket som helst af kravene 2-6, isoleret polypeptidmolekyle ifølge krav 7, isoleret CAR-molekyle ifølge krav 8 eller 9, vektor ifølge krav 10 eller celle ifølge krav 11 til anvendelse som et medikament.
17. Celle ifølge krav 11, der endvidere eksprimerer et inhibitorisk molekyle, der omfatter et første polypeptid, der omfatter mindst en del af et inhibitorisk molekyle, som er forbundet med et andet polypeptid, der omfatter et positivt signal fra et intracellulært signaleringsdomæne, eventuelt hvor det inhibitoriske molekyle omfatter et første polypeptid, der omfatter mindst en del af PD1, og et andet polypeptid, der omfatter et co-stimulerende domæne og et primært signaleringsdomæne.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361802629P | 2013-03-16 | 2013-03-16 | |
US201361838537P | 2013-06-24 | 2013-06-24 | |
PCT/US2014/029943 WO2014153270A1 (en) | 2013-03-16 | 2014-03-15 | Treatment of cancer using humanized anti-cd19 chimeric antigen receptor |
Publications (1)
Publication Number | Publication Date |
---|---|
DK2970482T3 true DK2970482T3 (da) | 2019-04-23 |
Family
ID=50680172
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK14722469.5T DK2970482T3 (da) | 2013-03-16 | 2014-03-15 | Behandling af cancer under anvendelse af humaniseret kimær anti-cd19-antigenreceptor |
DK19158368.1T DK3539986T3 (da) | 2013-03-16 | 2014-03-15 | Behandling af cancer under anvendelse af humaniseret kimær anti-cd19-antigenreceptor |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK19158368.1T DK3539986T3 (da) | 2013-03-16 | 2014-03-15 | Behandling af cancer under anvendelse af humaniseret kimær anti-cd19-antigenreceptor |
Country Status (25)
Country | Link |
---|---|
US (3) | US10221245B2 (da) |
EP (3) | EP3539986B1 (da) |
JP (4) | JP6466401B2 (da) |
KR (1) | KR102293062B1 (da) |
CN (2) | CN105392888B (da) |
AU (3) | AU2014236098B8 (da) |
BR (1) | BR112015021819A2 (da) |
CA (1) | CA2907100C (da) |
DK (2) | DK2970482T3 (da) |
ES (2) | ES2923397T3 (da) |
HK (1) | HK1218922A1 (da) |
HR (1) | HRP20220767T1 (da) |
HU (2) | HUE058832T2 (da) |
IL (1) | IL241261B (da) |
LT (2) | LT2970482T (da) |
MX (2) | MX2015013194A (da) |
MY (1) | MY187624A (da) |
PL (2) | PL3539986T3 (da) |
PT (2) | PT3539986T (da) |
RU (2) | RU2020100865A (da) |
SG (2) | SG11201506603PA (da) |
SI (1) | SI3539986T1 (da) |
TW (1) | TWI654206B (da) |
UY (1) | UY35468A (da) |
WO (1) | WO2014153270A1 (da) |
Families Citing this family (392)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130266551A1 (en) * | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
US9476095B2 (en) | 2011-04-15 | 2016-10-25 | The Johns Hopkins University | Safe sequencing system |
EA201491572A1 (ru) | 2012-02-22 | 2014-12-30 | Дзе Трастиз Оф Дзе Юниверсити Оф Пенсильвания | Композиции и способы получения устойчивой популяции t-клеток, используемых для лечения злокачественного новообразования |
EP3447495B2 (en) | 2012-10-29 | 2024-03-13 | The Johns Hopkins University | Papanicolaou test for ovarian and endometrial cancers |
RU2708032C2 (ru) | 2013-02-20 | 2019-12-03 | Новартис Аг | ЛЕЧЕНИЕ РАКА С ИСПОЛЬЗОВАНИЕМ ХИМЕРНОГО АНТИГЕНСПЕЦИФИЧЕСКОГО РЕЦЕПТОРА НА ОСНОВЕ ГУМАНИЗИРОВАННОГО АНТИТЕЛА ПРОТИВ EGFRvIII |
WO2014130635A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
EP2970426B1 (en) | 2013-03-15 | 2019-08-28 | Michael C. Milone | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
CA3225453A1 (en) | 2013-12-19 | 2015-06-25 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
EP3087101B1 (en) | 2013-12-20 | 2024-06-05 | Novartis AG | Regulatable chimeric antigen receptor |
AU2014368383B2 (en) | 2013-12-20 | 2020-01-16 | Cellectis | Method of engineering multi-input signal sensitive T cell for immunotherapy |
WO2015112626A1 (en) * | 2014-01-21 | 2015-07-30 | June Carl H | Enhanced antigen presenting ability of car t cells by co-introduction of costimulatory molecules |
WO2015120187A1 (en) | 2014-02-05 | 2015-08-13 | The University Of Chicago | Chimeric antigen receptors recognizing cancer-spevific tn glycopeptide variants |
ES2792849T3 (es) | 2014-02-10 | 2020-11-12 | Univ Emory | Expresión de polipéptido químico con receptores de linfocitos variables en células inmunes y usos para tratar el cáncer |
MX370272B (es) | 2014-03-19 | 2019-12-09 | Cellectis | Receptores de antigeno quimerico especifico de cd123 para inmunoterapia de cancer. |
HUE054588T2 (hu) | 2014-04-07 | 2021-09-28 | Novartis Ag | Rák kezelése CD19 elleni, kiméra antigénreceptor alkalmazásával |
CA2945308C (en) | 2014-04-10 | 2023-10-31 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Transgene genetic tags and methods of use |
JP2017514522A (ja) | 2014-05-02 | 2017-06-08 | エモリー ユニバーシティー | ヒト化可変性リンパ球受容体(vlr)および組成物ならびにそれに関連する使用 |
CN106459914B (zh) | 2014-05-15 | 2020-11-06 | 新加坡国立大学 | 经修饰的自然杀伤细胞及其用途 |
CN106536564B (zh) * | 2014-06-02 | 2021-08-31 | 美国卫生和人力服务部 | 靶向cd-19的嵌合抗原受体 |
CN107075483A (zh) | 2014-07-15 | 2017-08-18 | 朱诺治疗学股份有限公司 | 用于过继细胞治疗的工程改造的细胞 |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
AR101829A1 (es) | 2014-07-21 | 2017-01-18 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno cll-1 |
EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
MY181834A (en) | 2014-07-21 | 2021-01-08 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
CA2955154C (en) | 2014-07-21 | 2023-10-31 | Novartis Ag | Treatment of cancer using a cd33 chimeric antigen receptor |
RU2747457C2 (ru) | 2014-07-24 | 2021-05-05 | Блубёрд Био, Инк. | Химерные антигенные рецепторы к bcma |
EP4205749A1 (en) | 2014-07-31 | 2023-07-05 | Novartis AG | Subset-optimized chimeric antigen receptor-containing cells |
PL3183268T3 (pl) | 2014-08-19 | 2020-09-07 | Novartis Ag | Chimeryczny receptor antygenowy (CAR) anty-CD123 do zastosowania w leczeniu nowotworu złośliwego |
TWI751102B (zh) | 2014-08-28 | 2022-01-01 | 美商奇諾治療有限公司 | 對cd19具專一性之抗體及嵌合抗原受體 |
WO2016044605A1 (en) | 2014-09-17 | 2016-03-24 | Beatty, Gregory | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
CN107109368A (zh) * | 2014-10-07 | 2017-08-29 | 塞勒克提斯公司 | 用于调节car诱导的免疫细胞活性的方法 |
KR20170068504A (ko) * | 2014-10-08 | 2017-06-19 | 노파르티스 아게 | 키메라 항원 수용체 요법에 대한 치료 반응성을 예측하는 바이오마커 및 그의 용도 |
WO2016061368A1 (en) * | 2014-10-15 | 2016-04-21 | The Children's Hospital Of Philadelphia | Compositions and methods for treating b-lymphoid malignancies |
SG10202104804PA (en) | 2014-10-20 | 2021-06-29 | Juno Therapeutics Inc | Methods and compositions for dosing in adoptive cell therapy |
EP3212223B1 (en) | 2014-10-27 | 2021-08-18 | Fred Hutchinson Cancer Research Center | Compositions and methods for boosting the efficacy of adoptive cellular immunotherapy |
TWI735418B (zh) * | 2014-11-05 | 2021-08-11 | 美商奇諾治療有限公司 | 用於轉導作用及細胞處理之方法 |
US20180334490A1 (en) * | 2014-12-03 | 2018-11-22 | Qilong H. Wu | Methods for b cell preconditioning in car therapy |
ES2819553T3 (es) | 2014-12-03 | 2021-04-16 | Juno Therapeutics Inc | Métodos y composiciones para terapia celular adoptiva |
PT3628687T (pt) | 2014-12-12 | 2021-10-20 | Bluebird Bio Inc | Recetores do antigénio quimérico bcma |
US20170296623A1 (en) * | 2014-12-17 | 2017-10-19 | Cellectis | INHIBITORY CHIMERIC ANTIGEN RECEPTOR (iCAR OR N-CAR) EXPRESSING NON-T CELL TRANSDUCTION DOMAIN |
IL253149B2 (en) * | 2014-12-29 | 2023-11-01 | Novartis Ag | Methods for preparing cells expressing a chimeric receptor antigen |
US11382963B2 (en) | 2015-01-12 | 2022-07-12 | Pieris Pharmaceuticals Gmbh | Engineered T cells and uses therefor |
WO2016115482A1 (en) | 2015-01-16 | 2016-07-21 | Novartis Pharma Ag | Phosphoglycerate kinase 1 (pgk) promoters and methods of use for expressing chimeric antigen receptor |
GB201501004D0 (en) | 2015-01-21 | 2015-03-04 | Cancer Rec Tech Ltd | Inhibitors |
WO2016123143A1 (en) | 2015-01-26 | 2016-08-04 | The University Of Chicago | CAR T-CELLS RECOGNIZING CANCER-SPECIFIC IL 13Rα2 |
US10308719B2 (en) | 2015-01-26 | 2019-06-04 | The University Of Chicago | IL13Rα2 binding agents and use thereof in cancer treatment |
US11014989B2 (en) | 2015-01-26 | 2021-05-25 | Cellectis | Anti-CLL1 specific single-chain chimeric antigen receptors (scCARs) for cancer immunotherapy |
AU2016211438C1 (en) * | 2015-01-29 | 2021-03-04 | Regents Of The University Of Minnesota | Chimeric antigen receptors, compositions, and methods |
WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
WO2016149485A1 (en) * | 2015-03-17 | 2016-09-22 | The Regents Of The University Of California | Novel chemoimmunotherapy for epithelial cancer |
ES2876974T3 (es) | 2015-04-07 | 2021-11-15 | Novartis Ag | Combinación de terapia con receptor de antígeno quimérico y derivados de amino pirimidina |
EP4056588A1 (en) * | 2015-04-08 | 2022-09-14 | Novartis AG | Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car)- expressing cell |
CA2982996A1 (en) | 2015-04-17 | 2016-10-20 | David Maxwell Barrett | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
GB201507111D0 (en) * | 2015-04-27 | 2015-06-10 | Ucl Business Plc | Nucleic acid construct |
GB201507368D0 (en) * | 2015-04-30 | 2015-06-17 | Ucl Business Plc | Cell |
CA3155251A1 (en) | 2015-05-01 | 2016-11-10 | The Regents Of The University Of California | Glycan-dependent immunotherapeutic molecules |
CA2986254A1 (en) | 2015-05-18 | 2016-11-24 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
US20180161369A1 (en) | 2015-05-29 | 2018-06-14 | Fred Hutchinson Cancer Research Center | Compositions for cellular immunotherapy |
CN115927474A (zh) | 2015-06-19 | 2023-04-07 | 塞巴斯蒂安·科博尔德 | Pd-1-cd28融合蛋白及其在医学中的用途 |
MA42902A (fr) * | 2015-07-08 | 2018-05-16 | Univ Johns Hopkins | Lymphocytes infiltrant la moelle (mil) en tant que source de lymphocytes t pour une thérapie par des récepteurs chimériques d'un antigène (car) |
MA42895A (fr) | 2015-07-15 | 2018-05-23 | Juno Therapeutics Inc | Cellules modifiées pour thérapie cellulaire adoptive |
EP3744340A3 (en) | 2015-07-16 | 2021-03-03 | Biokine Therapeutics Ltd. | Compositions and methods for treating cancer |
AU2016297014B2 (en) | 2015-07-21 | 2021-06-17 | Novartis Ag | Methods for improving the efficacy and expansion of immune cells |
US10493139B2 (en) | 2015-07-24 | 2019-12-03 | Innovative Cellular Therapeutics CO., LTD. | Humanized anti-CD19 antibody and use thereof with chimeric antigen receptor |
EP3149046B1 (en) * | 2015-07-24 | 2020-02-26 | Innovative Cellular Therapeutics Co., Ltd. | Humanized anti-cd19 antibody and use thereof |
WO2017027392A1 (en) | 2015-08-07 | 2017-02-16 | Novartis Ag | Treatment of cancer using chimeric cd3 receptor proteins |
WO2017027291A1 (en) * | 2015-08-07 | 2017-02-16 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Bispecific car t-cells for solid tumor targeting |
CN105384825B (zh) * | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | 一种基于单域抗体的双特异性嵌合抗原受体及其应用 |
US11286531B2 (en) | 2015-08-11 | 2022-03-29 | The Johns Hopkins University | Assaying ovarian cyst fluid |
JP6887685B2 (ja) | 2015-08-12 | 2021-06-16 | 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 | ナノ粒子の細胞表面共役 |
CN106467906B (zh) * | 2015-08-20 | 2019-09-27 | 北京马力喏生物科技有限公司 | 构建体、转基因淋巴细胞及其制备方法和用途 |
US20180243340A1 (en) * | 2015-08-24 | 2018-08-30 | University Of Houston System | Combination therapy combining car + t cells with appropriately timed immunodulatory antibodies |
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 |
MA44909A (fr) * | 2015-09-15 | 2018-07-25 | Acerta Pharma Bv | Association thérapeutique d'un inhibiteur du cd19 et d'un inhibiteur de la btk |
US10265379B2 (en) * | 2015-09-16 | 2019-04-23 | Annabelle Rodriguez Oquendo | Use of recombinant lymphocyte activation gene-3 as a companion therapeutic for patients at risk for cardiovascular disease and other chronic inflammatory diseases |
JP6991131B2 (ja) * | 2015-09-22 | 2022-02-03 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | Hiv感染症を処置するためにt細胞を再度方向付ける方法 |
EP3569244A1 (en) * | 2015-09-23 | 2019-11-20 | CytoImmune Therapeutics, LLC | Flt3 directed car cells for immunotherapy |
JP2018534264A (ja) * | 2015-09-28 | 2018-11-22 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 自己免疫および同種免疫への治療的介入としてのキメラ抗原受容体(car)t細胞 |
EP3359562B1 (en) * | 2015-10-09 | 2019-12-04 | Miltenyi Biotec Technology, Inc. | Chimeric antigen receptors and methods of use |
PL3362470T3 (pl) | 2015-10-13 | 2022-02-21 | City Of Hope | Chimeryczne receptory antygenowe zawierające domenę chlorotoksyny |
CN107531793B (zh) * | 2015-10-13 | 2022-01-11 | 优瑞科生物技术公司 | 对人类cd19具有专一性的抗体药剂和其用途 |
US20180303935A1 (en) * | 2015-10-16 | 2018-10-25 | University Of Utah Research Foundation | A nanomaterial complex comprising graphene oxide associated with a therapeutic agent and methods of use |
EP3362569B1 (en) | 2015-10-16 | 2021-09-01 | Ludwig-Maximilians-Universität München | Cxcr6-transduced t cells for targeted tumor therapy |
WO2017079703A1 (en) | 2015-11-05 | 2017-05-11 | Juno Therapeutics, Inc. | Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy |
MA44314A (fr) | 2015-11-05 | 2018-09-12 | Juno Therapeutics Inc | Récepteurs chimériques contenant des domaines induisant traf, et compositions et méthodes associées |
CN105331585A (zh) * | 2015-11-13 | 2016-02-17 | 科济生物医药(上海)有限公司 | 携带pd-l1阻断剂的嵌合抗原受体修饰的免疫效应细胞 |
MX2018006245A (es) | 2015-11-18 | 2018-08-01 | Merck Sharp & Dohme | Proteinas de union a pd1 y/o lag3. |
EP3383419B1 (en) * | 2015-12-03 | 2022-08-03 | Juno Therapeutics, Inc. | Compositions and methods for reducing immune responses against chimeric antigen receptors |
AU2016363025B2 (en) | 2015-12-03 | 2021-04-08 | Juno Therapeutics, Inc. | Modified chimeric receptors and related compositions and methods |
MX2018006767A (es) | 2015-12-04 | 2019-03-14 | Novartis Ag | Composiciones y metodos para oncologia inmunologica. |
US11815514B2 (en) * | 2015-12-04 | 2023-11-14 | Juno Therapeutics, Inc. | Methods and compositions related to toxicity associated with cell therapy |
JP7082055B2 (ja) | 2015-12-22 | 2022-06-07 | ノバルティス アーゲー | 抗癌治療における組み合わせ使用のためのメソテリンキメラ抗原受容体(car)およびpd-l1阻害剤に対する抗体 |
CN109072195A (zh) | 2015-12-30 | 2018-12-21 | 诺华股份有限公司 | 具有增强功效的免疫效应细胞疗法 |
KR20180095719A (ko) | 2016-01-11 | 2018-08-27 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | 키메라 단백질 및 면역요법 방법 |
CN105950645A (zh) * | 2016-01-11 | 2016-09-21 | 灏灵赛奥(天津)生物科技有限公司 | Car-cd19抗原受体的人源化融合基因片段、其构建方法及应用 |
US9856497B2 (en) | 2016-01-11 | 2018-01-02 | The Board Of Trustee Of The Leland Stanford Junior University | Chimeric proteins and methods of regulating gene expression |
CN107034193B (zh) * | 2016-02-03 | 2020-06-05 | 北京马力喏生物科技有限公司 | 治疗b细胞白血病及b细胞淋巴瘤的治疗组合物 |
US20200281973A1 (en) | 2016-03-04 | 2020-09-10 | Novartis Ag | Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore |
EP3430549A1 (en) | 2016-03-16 | 2019-01-23 | Juno Therapeutics, Inc. | Methods for adaptive design of a treatment regimen and related treatments |
MA43758A (fr) | 2016-03-16 | 2018-11-28 | Yuan Ji | Procédés pour déterminer le dosage d'un agent thérapeutique et traitements associés |
EP3430038B1 (en) | 2016-03-18 | 2021-06-16 | Fred Hutchinson Cancer Research Center | Compositions and methods for cd20 immunotherapy |
EP4015536A1 (en) | 2016-03-22 | 2022-06-22 | Seattle Children's Hospital (DBA Seattle Children's Research Institute) | Early intervention methods to prevent or ameliorate toxicity |
WO2017165683A1 (en) | 2016-03-23 | 2017-09-28 | Novartis Ag | Cell secreted minibodies and uses thereof |
EP4286522A3 (en) * | 2016-03-23 | 2024-02-28 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Fusion proteins of pd-1 and 4-1bb |
JP7208010B2 (ja) * | 2016-03-29 | 2023-01-18 | ユニバーシティ オブ サザン カリフォルニア | 癌を標的とするキメラ抗原受容体 |
CN109069537B (zh) * | 2016-04-04 | 2022-04-15 | 亘喜生物科技(上海)有限公司 | 共刺激结构域中具有重复结合基序的car |
EP3443001A4 (en) * | 2016-04-11 | 2020-04-29 | Obsidian Therapeutics, Inc. | REGULATED BIOCIRCUIT SYSTEMS |
KR20180134385A (ko) | 2016-04-15 | 2018-12-18 | 노파르티스 아게 | 선택적 단백질 발현을 위한 조성물 및 방법 |
CA3022267A1 (en) | 2016-05-04 | 2017-11-09 | Fred Hutchinson Cancer Research Center | Cell-based neoantigen vaccines and uses thereof |
CN105950663B (zh) * | 2016-05-17 | 2019-04-02 | 上海优卡迪生物医药科技有限公司 | 一种靶向cd30的复制缺陷性重组慢病毒car-t转基因载体及其构建方法和应用 |
CN105950662B (zh) * | 2016-05-17 | 2019-04-30 | 上海优卡迪生物医药科技有限公司 | 一种靶向cd22的复制缺陷性重组慢病毒car-t转基因载体及其构建方法和应用 |
CN105969805B (zh) * | 2016-05-17 | 2019-03-29 | 上海优卡迪生物医药科技有限公司 | 一种靶向Mesothelin的复制缺陷性重组慢病毒CAR-T转基因载体及其构建方法和应用 |
CN105950664B (zh) * | 2016-05-17 | 2019-03-29 | 上海优卡迪生物医药科技有限公司 | 一种靶向cd123的复制缺陷性重组慢病毒car-t转基因载体及其构建方法和应用 |
US20210177896A1 (en) | 2016-06-02 | 2021-06-17 | Novartis Ag | Therapeutic regimens for chimeric antigen receptor (car)- expressing cells |
CA3026453A1 (en) | 2016-06-03 | 2017-12-07 | Memorial Sloan-Kettering Cancer Center | Adoptive cell therapies as early treatment options |
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 |
JP2019517803A (ja) * | 2016-06-14 | 2019-06-27 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 疾患を処置するための遺伝子改変された細胞、組織、および臓器 |
CN107523548A (zh) * | 2016-06-20 | 2017-12-29 | 上海细胞治疗研究院 | 一种高效稳定表达抗体的t细胞及其用途 |
CN107523549A (zh) * | 2016-06-20 | 2017-12-29 | 上海细胞治疗研究院 | 一种高效稳定表达激活型抗体的car‑t细胞及其用途 |
CN106117366A (zh) * | 2016-06-24 | 2016-11-16 | 安徽未名细胞治疗有限公司 | 一种cd19特异性嵌合抗原受体及其编码基因、应用 |
MA45491A (fr) | 2016-06-27 | 2019-05-01 | Juno Therapeutics Inc | Épitopes à restriction cmh-e, molécules de liaison et procédés et utilisations associés |
CA3028002A1 (en) | 2016-06-27 | 2018-01-04 | Juno Therapeutics, Inc. | Method of identifying peptide epitopes, molecules that bind such epitopes and related uses |
BR112018077375A2 (pt) | 2016-06-30 | 2019-10-01 | F. Hoffmann-La Roche Ag | kits, moléculas de anticorpo biespecífico trivalente, composição farmacêutica, vetor de expressão, célula hospedeira e método para a produção de uma molécula de anticorpo biespecífico trivalente |
CN106267409B (zh) * | 2016-07-01 | 2019-02-01 | 翁炳焕 | 艾滋病生物治疗反应器 |
CN106178163B (zh) * | 2016-07-01 | 2019-02-01 | 翁炳焕 | 艾滋病生物细胞免疫治疗仪 |
CN107586341A (zh) * | 2016-07-08 | 2018-01-16 | 生命序有限公司 | 重组免疫检查点受体及免疫检查点抑制分子的共表达及应用 |
CN107586342A (zh) * | 2016-07-08 | 2018-01-16 | 生命序有限公司 | 重组免疫检查点受体及其应用 |
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 |
US11365252B2 (en) | 2016-07-20 | 2022-06-21 | University Of Utah Research Foundation | CD229 CAR T cells and methods of use thereof |
CN106011174B (zh) * | 2016-07-26 | 2019-12-13 | 天晴干细胞股份有限公司 | 一种通用型慢病毒载体及其制备方法 |
CN118021943A (zh) * | 2016-07-28 | 2024-05-14 | 诺华股份有限公司 | 嵌合抗原受体和pd-1抑制剂的组合疗法 |
KR20230107408A (ko) | 2016-07-29 | 2023-07-14 | 주노 쎄러퓨티크스 인코퍼레이티드 | 항-cd19 항체에 대한 항-이디오타입 항체 |
EP3490590A2 (en) | 2016-08-01 | 2019-06-05 | Novartis AG | Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule |
JP7109789B2 (ja) | 2016-08-02 | 2022-08-01 | ティーシーアール2 セラピューティクス インク. | 融合タンパク質を使用したtcrの再プログラム化のための組成物及び方法 |
CN106350487B (zh) * | 2016-09-13 | 2019-01-25 | 北京多赢时代转化医学研究院 | 联合制备car-nk细胞和car-nkt细胞的方法 |
CN106399242B (zh) * | 2016-09-13 | 2019-01-22 | 北京多赢时代转化医学研究院 | 联合制备CAR-Vγ9Vδ2T细胞和CAR-NKT细胞的方法 |
WO2018057585A1 (en) | 2016-09-21 | 2018-03-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptor (car) that targets chemokine receptor ccr4 and its use |
CN106317228A (zh) * | 2016-09-28 | 2017-01-11 | 李华顺 | 一种嵌合抗原受体分子及其应用 |
CN109844126A (zh) | 2016-09-28 | 2019-06-04 | 诺华股份有限公司 | 基于多孔膜的大分子递送系统 |
EP4353319A3 (en) | 2016-09-28 | 2024-06-05 | Atossa Therapeutics, Inc. | Methods of adoptive cell therapy |
CA3038968A1 (en) | 2016-09-30 | 2018-04-05 | Genvec, Inc. | Adenovectors for delivery of therapeutic genetic material into t cells |
JP7217970B2 (ja) | 2016-10-07 | 2023-02-06 | ティーシーアール2 セラピューティクス インク. | 融合タンパク質を用いてt細胞受容体をリプログラミングするための組成物及び方法 |
CN117866991A (zh) | 2016-10-07 | 2024-04-12 | 诺华股份有限公司 | 用于治疗癌症的嵌合抗原受体 |
WO2018071873A2 (en) | 2016-10-13 | 2018-04-19 | Juno Therapeutics, Inc. | Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators |
CN107988164B (zh) | 2016-10-26 | 2020-07-07 | 阿思科力(苏州)生物科技有限公司 | 一种pd-1 car nk-92细胞及其制备方法与应用 |
EP3534940A1 (en) | 2016-11-03 | 2019-09-11 | Juno Therapeutics, Inc. | Combination therapy of a cell based therapy and a microglia inhibitor |
JP2019532997A (ja) | 2016-11-03 | 2019-11-14 | ジュノー セラピューティクス インコーポレイテッド | T細胞療法とbtk阻害剤との併用療法 |
WO2018098365A2 (en) | 2016-11-22 | 2018-05-31 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
WO2018102612A1 (en) | 2016-12-02 | 2018-06-07 | Juno Therapeutics, Inc. | Engineered b cells and related compositions and methods |
MA46963A (fr) | 2016-12-03 | 2019-10-09 | Juno Therapeutics Inc | Méthodes pour déterminer le dosage de céllules car-t |
EP3548083A1 (en) | 2016-12-03 | 2019-10-09 | Juno Therapeutics, Inc. | Methods for modulation of car-t cells |
EP3548046A2 (en) | 2016-12-03 | 2019-10-09 | Juno Therapeutics, Inc. | Methods and compositions for use of therapeutic t cells in combination with kinase inhibitors |
AU2017375630B2 (en) | 2016-12-12 | 2023-12-21 | 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 |
EP3556772A4 (en) * | 2016-12-13 | 2020-09-09 | Carsgen Therapeutics Ltd | HUMANIZED ANTI-CD19 ANTIBODY AND TARGETING IMMUNE EFFICIENT CELL CD19 |
CN108250301A (zh) | 2016-12-29 | 2018-07-06 | 天津天锐生物科技有限公司 | 一种多靶点嵌合抗原受体 |
EP3609536B1 (en) * | 2017-01-05 | 2022-03-09 | Innovative Cellular Therapeutics Holdings, Ltd. | Humanized anti-cd19 antibody and use thereof with chimeric antigen receptor |
EP3346001A1 (en) * | 2017-01-06 | 2018-07-11 | TXCell | Monospecific regulatory t cell population with cytotoxicity for b cells |
EP3568406A4 (en) * | 2017-01-10 | 2020-10-21 | The General Hospital Corporation | T-CELLS WITH EXPRESSION OF A CHIMERIC ANTIGEN RECEPTOR |
WO2018132518A1 (en) | 2017-01-10 | 2018-07-19 | Juno Therapeutics, Inc. | Epigenetic analysis of cell therapy and related methods |
CN107058390A (zh) * | 2017-01-17 | 2017-08-18 | 上海交通大学医学院附属第九人民医院 | 一种慢病毒载体、重组慢病毒质粒、病毒及病毒的应用 |
EP4043485A1 (en) | 2017-01-26 | 2022-08-17 | Novartis AG | Cd28 compositions and methods for chimeric antigen receptor therapy |
JP2020506700A (ja) | 2017-01-31 | 2020-03-05 | ノバルティス アーゲー | 多重特異性を有するキメラt細胞受容体タンパク質を用いた癌の治療 |
CN110612119A (zh) | 2017-02-07 | 2019-12-24 | 西雅图儿童医院(Dba西雅图儿童研究所) | 磷脂醚(ple)car t细胞肿瘤靶向(ctct)剂 |
CN110461335A (zh) | 2017-02-17 | 2019-11-15 | 弗雷德哈钦森癌症研究中心 | 用于治疗bcma相关癌症和自身免疫性失调的联合疗法 |
US20200191774A1 (en) | 2017-02-27 | 2020-06-18 | Juno Therapeutics, Inc. | Compositions, articles of manufacture and methods related to dosing in cell therapy |
WO2018160731A1 (en) | 2017-02-28 | 2018-09-07 | Novartis Ag | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
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 |
AU2018234640B2 (en) | 2017-03-14 | 2024-03-14 | Juno Therapeutics, Inc. | Methods for cryogenic storage |
RU2019133280A (ru) | 2017-03-22 | 2021-04-22 | Новартис Аг | Композиции и способы для иммуноонкологии |
US11896616B2 (en) | 2017-03-27 | 2024-02-13 | National University Of Singapore | Stimulatory cell lines for ex vivo expansion and activation of natural killer cells |
MX2019011514A (es) | 2017-03-27 | 2020-01-27 | Nat Univ Singapore | Receptores quimericos nkg2d truncados y usos de los mismos en inmunoterapia con celulas asesinas naturales. |
CN107058232B (zh) * | 2017-04-12 | 2018-03-30 | 上海优卡迪生物医药科技有限公司 | 胆固醇转脂酶soat1被抑制的car‑t细胞及其制备方法和应用 |
MX2019012189A (es) | 2017-04-14 | 2020-12-10 | Juno Therapeutics Inc | Metodos para valorar la glucosilacion de la superficie celular. |
CN108728459B (zh) * | 2017-04-24 | 2023-08-04 | 上海恒润达生生物科技股份有限公司 | 靶向cd19的嵌合抗原受体并联合表达il-15的方法和用途 |
JOP20180042A1 (ar) * | 2017-04-24 | 2019-01-30 | Kite Pharma Inc | نطاقات ربط مولد ضد متوافقة مع البشر وطرق الاستخدام |
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 |
FI3618842T3 (fi) | 2017-05-01 | 2023-12-15 | Juno Therapeutics Inc | Soluterapian ja immunomodulatorisen yhdisteen yhdistelmä |
CA3063563A1 (en) | 2017-05-24 | 2018-11-29 | Effector Therapeutics, Inc. | Compositions and methods for an improved antitumor immune response |
CN111225675B (zh) | 2017-06-02 | 2024-05-03 | 朱诺治疗学股份有限公司 | 使用过继细胞疗法治疗的制品和方法 |
CN108977453A (zh) | 2017-06-02 | 2018-12-11 | 阿思科力(苏州)生物科技有限公司 | 一种以robo1为靶点的嵌合抗原受体细胞及其制备和应用 |
SG11201912010XA (en) | 2017-06-12 | 2020-01-30 | Obsidian Therapeutics Inc | Pde5 compositions and methods for immunotherapy |
US20220225597A1 (en) | 2017-06-29 | 2022-07-21 | Juno Therapeutics, Inc. | Mouse model for assessing toxicities associated with immunotherapies |
JP2020530277A (ja) | 2017-06-30 | 2020-10-22 | セレクティスCellectis | 反復投与のための細胞免疫療法 |
EP3662055A1 (en) * | 2017-08-02 | 2020-06-10 | Autolus Limited | Cells expressing a chimeric antigen receptor or engineered tcr and comprising a nucleotide sequence which is selectively expressed |
EP3665308A1 (en) | 2017-08-07 | 2020-06-17 | The Johns Hopkins University | Methods and materials for assessing and treating cancer |
CN107383196B (zh) * | 2017-08-30 | 2019-12-17 | 广州百暨基因科技有限公司 | 人源化抗cd19的抗原结合片段 |
WO2019046832A1 (en) | 2017-09-01 | 2019-03-07 | Juno Therapeutics, Inc. | GENE EXPRESSION AND EVALUATION OF RISK OF DEVELOPMENT OF TOXICITY FOLLOWING CELL THERAPY |
US10501539B2 (en) * | 2017-09-15 | 2019-12-10 | Lentigen Technology Inc. | Compositions and methods for treating cancer with anti-CD19 immunotherapy |
WO2019052577A1 (zh) | 2017-09-18 | 2019-03-21 | 博雅辑因(北京)生物科技有限公司 | 一种基因编辑t细胞及其用途 |
KR20200055037A (ko) | 2017-09-19 | 2020-05-20 | 메사추세츠 인스티튜트 오브 테크놀로지 | 키메라 항원 수용체 t 세포 요법을 위한 조성물 및 그의 용도 |
US20200354452A1 (en) * | 2017-09-29 | 2020-11-12 | City Of Hope | Cars and bispecific antibodies for treatment of mantle cell lymphoma |
AU2018346955A1 (en) | 2017-10-13 | 2020-04-30 | Harpoon Therapeutics, Inc. | B cell maturation antigen binding proteins |
KR20200086278A (ko) | 2017-10-18 | 2020-07-16 | 노파르티스 아게 | 선택적 단백질 분해를 위한 조성물 및 방법 |
CA3078270A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
MX2020004202A (es) | 2017-10-30 | 2020-08-13 | Neuropore Therapies Inc | Fenil sulfonil fenil triazol tionas sustituidas y usos de las mismas. |
MX2020004516A (es) * | 2017-10-31 | 2020-10-20 | Allogene Therapeutics Inc | Metodos y composiciones para la dosificacion de celulas t con receptor de antigeno quimerico alogenicas. |
WO2019089798A1 (en) | 2017-10-31 | 2019-05-09 | Novartis Ag | Anti-car compositions and methods |
US20210254000A1 (en) | 2017-11-01 | 2021-08-19 | Juno Therapeutics, Inc. | Process for producing a t cell composition |
WO2019089858A2 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
BR112020008340A2 (pt) | 2017-11-01 | 2020-11-17 | Juno Therapeutics Inc | processo para gerar composições terapêuticas de células modificadas |
WO2019089848A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
US11851679B2 (en) | 2017-11-01 | 2023-12-26 | Juno Therapeutics, Inc. | Method of assessing activity of recombinant antigen receptors |
AU2018360800A1 (en) | 2017-11-01 | 2020-05-14 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for B-cell maturation antigen (BCMA) |
EP3706754A1 (en) | 2017-11-06 | 2020-09-16 | Juno Therapeutics, Inc. | Combination of a cell therapy and a gamma secretase inhibitor |
WO2019094498A1 (en) * | 2017-11-07 | 2019-05-16 | City Of Hope | Treatment of cns lymphoma and systemic lymphoma with intracerebroventricularly administered cd19 car |
WO2019094404A1 (en) * | 2017-11-07 | 2019-05-16 | Temple University-Of The Commonwealth System Of Higher Education | Compositions and methods for improved t cells |
US11802163B2 (en) | 2017-11-10 | 2023-10-31 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptors targeting glypican-3 or mesothelin |
JP2021502979A (ja) | 2017-11-15 | 2021-02-04 | ノバルティス アーゲー | Bcmaターゲティングキメラ抗原受容体、cd19ターゲティングキメラ抗原受容体及び併用療法 |
US20200209240A1 (en) * | 2017-11-20 | 2020-07-02 | Julius-Maximilians-Universität Würzburg | Cd19cart cells eliminate myeloma cells that express very low levels of cd19 |
CN109836493A (zh) * | 2017-11-25 | 2019-06-04 | 深圳宾德生物技术有限公司 | 一种靶向cd19的单链抗体、嵌合抗原受体t细胞及其制备方法和应用 |
TW201925782A (zh) | 2017-11-30 | 2019-07-01 | 瑞士商諾華公司 | 靶向bcma之嵌合抗原受體及其用途 |
EP3716980A1 (en) | 2017-12-01 | 2020-10-07 | Juno Therapeutics, Inc. | Methods for dosing and for modulation of genetically engineered cells |
AU2018379502A1 (en) * | 2017-12-06 | 2020-06-18 | Abclon Inc. | Antibody or antigen binding fragment thereof for specifically recognizing B cell malignancy, chimeric antigen receptor comprising same, and use thereof |
SG11202005272SA (en) | 2017-12-08 | 2020-07-29 | Juno Therapeutics Inc | Process for producing a composition of engineered t cells |
US20210207080A1 (en) | 2017-12-08 | 2021-07-08 | Juno Therapeutics, Inc. | Serum-free media formulation for culturing cells and methods of use thereof |
CN107880128B (zh) * | 2017-12-21 | 2021-03-02 | 常州费洛斯药业科技有限公司 | 一种抗cd19的全人源抗体或抗体片段及其方法和应用 |
CN109053899B (zh) | 2017-12-22 | 2021-11-16 | 湖南远泰生物技术有限公司 | 一种含人转铁蛋白抗原表位序列的嵌合体抗原受体 |
CN111683971A (zh) * | 2017-12-23 | 2020-09-18 | 宇越生医科技股份有限公司 | 医药重组受体组成物及方法 |
EP3737408A1 (en) | 2018-01-08 | 2020-11-18 | Novartis AG | Immune-enhancing rnas for combination with chimeric antigen receptor therapy |
EP3586852B8 (en) * | 2018-01-11 | 2021-04-28 | Innovative Cellular Therapeutics Inc. | Modified cell expansion and uses thereof |
US10561686B2 (en) | 2018-01-12 | 2020-02-18 | Innovative Cellular Therapeutics CO., LTD. | Modified cell expansion and uses thereof |
US11679129B2 (en) * | 2018-01-12 | 2023-06-20 | Curocell, Inc. | Enhanced immune cells using dual shRNA and composition including the same |
JP2021512147A (ja) | 2018-01-22 | 2021-05-13 | エンドサイト・インコーポレイテッドEndocyte, Inc. | Car t細胞の使用方法 |
CN108017717B (zh) * | 2018-01-24 | 2019-08-16 | 首都医科大学宣武医院 | 一种用于体外高效定向扩增的嵌合抗原受体及其应用 |
CN110093359B (zh) * | 2018-01-29 | 2023-10-13 | 华南生物医药研究院 | 含cd3启动子序列和car序列的可分离的核酸及应用 |
AU2019215031A1 (en) | 2018-01-31 | 2020-08-20 | Novartis Ag | Combination therapy using a chimeric antigen receptor |
CN111801104A (zh) * | 2018-02-06 | 2020-10-20 | 西雅图儿童医院(Dba西雅图儿童研究所) | Car-t细胞的封闭系统制造过程 |
CN111094358A (zh) * | 2018-02-11 | 2020-05-01 | 江苏恒瑞医药股份有限公司 | 一种分离的嵌合抗原受体以及包含其的修饰t细胞及用途 |
US20200399383A1 (en) | 2018-02-13 | 2020-12-24 | Novartis Ag | Chimeric antigen receptor therapy in combination with il-15r and il15 |
WO2019159193A1 (en) * | 2018-02-13 | 2019-08-22 | Indian Institute Of Technology Bombay | Novel humanized anti-cd19 chimeric antigen receptor, its nucelic acid sequence and its preparation |
US20210046159A1 (en) | 2018-03-09 | 2021-02-18 | Ospedale San Raffaele S.R.L. | Il-1 antagonist and toxicity induced by cell therapy |
SG11202008796VA (en) * | 2018-03-14 | 2020-10-29 | The United States Of America As Represented By The Secretary | Anti-cd33 chimeric antigen receptors and their uses |
US10751399B2 (en) * | 2018-03-20 | 2020-08-25 | Cho Pharma Usa, Inc. | Chimeric antigen receptors that bind to SSEA4 and uses thereof |
WO2019200250A1 (en) | 2018-04-13 | 2019-10-17 | Velculescu Victor E | Non-invasive detection of response to a targeted therapy |
WO2019200252A1 (en) | 2018-04-13 | 2019-10-17 | The Johns Hopkins University | Non-invasive detection of response to immunotherapy |
US10869888B2 (en) | 2018-04-17 | 2020-12-22 | Innovative Cellular Therapeutics CO., LTD. | Modified cell expansion and uses thereof |
US20210047405A1 (en) | 2018-04-27 | 2021-02-18 | Novartis Ag | Car t cell therapies with enhanced efficacy |
EP3788369A1 (en) | 2018-05-01 | 2021-03-10 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
CN112805563A (zh) | 2018-05-18 | 2021-05-14 | 约翰·霍普金斯大学 | 用于评估和/或治疗癌症的无细胞dna |
US20210213063A1 (en) | 2018-05-25 | 2021-07-15 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
JP7398396B2 (ja) | 2018-06-01 | 2023-12-14 | ノバルティス アーゲー | Bcmaに対する結合分子及びその使用 |
WO2019232510A1 (en) * | 2018-06-01 | 2019-12-05 | Kite Pharma, Inc. | Chimeric antigen receptor t cell therapy |
MX2020013017A (es) * | 2018-06-01 | 2021-03-02 | Mayo Found Medical Education & Res | Materiales y metodos para tratar cancer. |
EP3802825A1 (en) | 2018-06-08 | 2021-04-14 | Intellia Therapeutics, Inc. | Compositions and methods for immunooncology |
AU2019284911A1 (en) | 2018-06-13 | 2020-12-17 | Novartis Ag | BCMA chimeric antigen receptors and uses thereof |
KR20190141511A (ko) * | 2018-06-14 | 2019-12-24 | 주식회사 녹십자랩셀 | 신규 펩티드, 이를 포함하는 키메라 항원 수용체 및 이를 발현하는 면역 세포 |
WO2019246546A1 (en) * | 2018-06-22 | 2019-12-26 | The General Hospital Corporation | Chimeric antigen receptors targeting cd37 and cd19 |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
CA3107383A1 (en) | 2018-07-23 | 2020-01-30 | Magenta Therapeutics, Inc. | Use of anti-cd5 antibody drug conjugate (adc) in allogeneic cell therapy |
CN110819679A (zh) * | 2018-08-07 | 2020-02-21 | 上海恒润达生生物科技有限公司 | 一种评估cart细胞体内代谢的方法 |
EA202190469A1 (ru) | 2018-08-09 | 2021-06-28 | Джуно Терапьютикс, Инк. | Способы оценки интегрированных нуклеиновых кислот |
US20220348682A1 (en) | 2018-08-30 | 2022-11-03 | Innovative Cellular Therapeutics Holdings, Ltd. | Chimeric antigen receptor cells for treating solid tumor |
TW202026006A (zh) * | 2018-08-30 | 2020-07-16 | 美商Tcr2療法股份有限公司 | 使用融合蛋白進行tcr再程式化之組成物及方法 |
EP3844265A2 (en) | 2018-08-31 | 2021-07-07 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
WO2020043899A1 (en) | 2018-08-31 | 2020-03-05 | Invectys | Chimeric antigen receptors against multiple hla-g isoforms |
SG11202101825QA (en) | 2018-08-31 | 2021-03-30 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
CA3114038A1 (en) | 2018-09-25 | 2020-04-02 | Harpoon Therapeutics, Inc. | Dll3 binding proteins and methods of use |
CA3113618A1 (en) | 2018-09-28 | 2020-04-02 | Massachusetts Institute Of Technology | Collagen-localized immunomodulatory molecules and methods thereof |
US20220047633A1 (en) | 2018-09-28 | 2022-02-17 | Novartis Ag | Cd22 chimeric antigen receptor (car) therapies |
WO2020069409A1 (en) | 2018-09-28 | 2020-04-02 | Novartis Ag | Cd19 chimeric antigen receptor (car) and cd22 car combination therapies |
SG11202104355SA (en) | 2018-10-31 | 2021-05-28 | Juno Therapeutics Gmbh | Methods for selection and stimulation of cells and apparatus for same |
JP2022512913A (ja) | 2018-11-06 | 2022-02-07 | 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t細胞を作製するための方法 |
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 |
US10918667B2 (en) | 2018-11-20 | 2021-02-16 | Innovative Cellular Therapeutics CO., LTD. | Modified cell expressing therapeutic agent and uses thereof |
JP7232547B2 (ja) * | 2018-11-29 | 2023-03-03 | ジョージアン ルイジアメイ バイオテック カンパニー リミテッド | CDR1領域に突然変異したヒト化CD19 scFvを有するCAR-T細胞 |
KR20210117260A (ko) | 2018-11-30 | 2021-09-28 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법을 사용한 치료방법 |
MX2021006244A (es) | 2018-11-30 | 2021-09-10 | Juno Therapeutics Inc | Metodos de dosificacion y tratamiento de canceres de celulas b en terapia celular adoptiva. |
EP3893899A2 (en) | 2018-12-12 | 2021-10-20 | Kite Pharma, Inc. | Chimeric antigen receptors and car-t cells and methods of use |
WO2020124021A1 (en) * | 2018-12-13 | 2020-06-18 | The General Hospital Corporation | Chimeric antigen receptors targeting cd79b and cd19 |
DK3898946T3 (da) | 2018-12-19 | 2023-05-01 | Inst Nat Sante Rech Med | Mukosa-associerede invariante t- (mait) celler med ekspression af kimære antigenreceptorer |
BR112021011874A2 (pt) | 2018-12-20 | 2021-09-08 | Novartis Ag | Regime de dosagem e combinação farmacêutica compreendendo derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona |
CN109734813B (zh) * | 2019-01-28 | 2022-06-17 | 广东昭泰体内生物医药科技有限公司 | 一种嵌合抗原受体及其应用 |
CN113710253A (zh) * | 2019-02-04 | 2021-11-26 | 普洛迈博生物技术公司 | 编码嵌合抗原受体和il-6或检查点抑制剂的短发夹rna序列的核酸序列 |
WO2020163448A1 (en) * | 2019-02-06 | 2020-08-13 | The Regents Of The University Of Michigan | Chimeric antigen receptors targeting abnormal glycobiology |
CN113329792B (zh) | 2019-02-15 | 2024-06-28 | 诺华股份有限公司 | 取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
CN113490528A (zh) | 2019-02-15 | 2021-10-08 | 诺华股份有限公司 | 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
SG11202107825WA (en) | 2019-02-25 | 2021-09-29 | Novartis Ag | Mesoporous silica particles compositions for viral delivery |
WO2020180882A1 (en) * | 2019-03-05 | 2020-09-10 | Nkarta, Inc. | Cd19-directed chimeric antigen receptors and uses thereof in immunotherapy |
SG11202109172TA (en) | 2019-03-08 | 2021-09-29 | Obsidian Therapeutics Inc | Human carbonic anhydrase 2 compositions and methods for tunable regulation |
EP3942025A1 (en) | 2019-03-21 | 2022-01-26 | Novartis AG | Car-t cell therapies with enhanced efficacy |
EP3952886A1 (en) | 2019-04-10 | 2022-02-16 | Elevatebio Technologies, Inc | Flt3-specific chimeric antigen receptors and methods of using the same |
US20220168389A1 (en) | 2019-04-12 | 2022-06-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
EP3959320A1 (en) | 2019-04-24 | 2022-03-02 | Novartis AG | Compositions and methods for selective protein degradation |
CA3139965A1 (en) | 2019-06-07 | 2020-12-10 | Ivie AIFUWA | Automated t cell culture |
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 |
CN112390891B (zh) * | 2019-08-14 | 2022-06-03 | 苏州方德门达新药开发有限公司 | 嵌合抗原受体及其构建方法和应用 |
EP4017527A1 (en) | 2019-08-22 | 2022-06-29 | Juno Therapeutics, Inc. | Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods |
EP4028413A1 (en) | 2019-09-10 | 2022-07-20 | Obsidian Therapeutics, Inc. | Ca2-il15 fusion proteins for tunable regulation |
WO2021061648A1 (en) | 2019-09-23 | 2021-04-01 | Massachusetts Institute Of Technology | Methods and compositions for stimulation of endogenous t cell responses |
AU2020377043A1 (en) | 2019-10-30 | 2022-06-02 | Juno Therapeutics Gmbh | Cell selection and/or stimulation devices and methods of use |
CN114945382A (zh) | 2019-11-26 | 2022-08-26 | 诺华股份有限公司 | Cd19和cd22嵌合抗原受体及其用途 |
BR112022010206A2 (pt) | 2019-11-26 | 2022-11-29 | Novartis Ag | Receptores de antígeno quiméricos e usos dos mesmos |
EP4070097A1 (en) | 2019-12-06 | 2022-10-12 | Juno Therapeutics, Inc. | Methods related to toxicity and response associated with cell therapy for treating b cell malignancies |
KR20220122656A (ko) | 2019-12-06 | 2022-09-02 | 주노 쎄러퓨티크스 인코퍼레이티드 | Gprc5d-표적화 결합 도메인에 대한 항-이디오타입 항체 및 관련 조성물 및 방법 |
CN115916817A (zh) | 2019-12-06 | 2023-04-04 | 朱诺治疗学股份有限公司 | 针对bcma靶向结合结构域的抗独特型抗体及相关组合物和方法 |
CA3165399A1 (en) | 2019-12-20 | 2021-06-24 | Novartis Ag | Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
CN114901813A (zh) | 2019-12-30 | 2022-08-12 | 博雅缉因(北京)生物科技有限公司 | 一种靶向t细胞淋巴瘤细胞的通用型car-t及其制备方法和应用 |
WO2021136415A1 (zh) | 2019-12-30 | 2021-07-08 | 博雅辑因(北京)生物科技有限公司 | 一种纯化ucart细胞的方法与应用 |
JP2023511408A (ja) | 2020-01-23 | 2023-03-17 | ザ チルドレンズ メディカル センター コーポレーション | ヒト多能性幹細胞からのストロマフリーt細胞分化法 |
EP4104187A1 (en) | 2020-02-14 | 2022-12-21 | 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 |
WO2021173985A2 (en) | 2020-02-27 | 2021-09-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
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 |
JP2023516632A (ja) | 2020-02-28 | 2023-04-20 | 武田薬品工業株式会社 | 多能性幹細胞からナチュラルキラー細胞を産生するための方法 |
US20230085724A1 (en) | 2020-03-05 | 2023-03-23 | Neotx Therapeutics Ltd. | Methods and compositions for treating cancer with immune cells |
CN115768464A (zh) | 2020-03-10 | 2023-03-07 | 麻省理工学院 | 产生工程化记忆样nk细胞及其组合物的方法 |
BR112022017924A2 (pt) | 2020-03-10 | 2022-12-20 | Massachusetts Inst Technology | Composições e métodos para imunoterapia de câncer npm1c-positivo |
CN113402612A (zh) | 2020-03-17 | 2021-09-17 | 西比曼生物科技(香港)有限公司 | 靶向cd19和cd20的联合嵌合抗原受体及其应用 |
CN111484561A (zh) * | 2020-04-07 | 2020-08-04 | 北京荣瑷医学生物科技有限责任公司 | 一种靶向于cd19分子的嵌合抗原受体 |
CN111411085A (zh) * | 2020-04-10 | 2020-07-14 | 格源致善(上海)生物科技有限公司 | 一种嵌合抗原受体t细胞及其应用 |
KR20230015921A (ko) | 2020-04-28 | 2023-01-31 | 주노 쎄러퓨티크스 인코퍼레이티드 | Bcma-지시된 t 세포 요법 및 면역 조절 화합물의 조합 |
WO2021221782A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Chimeric antigen receptor-targeting ligands and uses thereof |
US20210340524A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Methods for identifying chimeric antigen receptor-targeting ligands and uses thereof |
US20230178239A1 (en) | 2020-05-13 | 2023-06-08 | Juno Therapeutics, Inc. | Methods of identifying features associated with clinical response and uses thereof |
WO2021231661A2 (en) | 2020-05-13 | 2021-11-18 | Juno Therapeutics, Inc. | Process for producing donor-batched cells expressing a recombinant receptor |
US20230332104A1 (en) | 2020-06-11 | 2023-10-19 | Novartis Ag | Zbtb32 inhibitors and uses thereof |
CA3182346A1 (en) | 2020-06-23 | 2021-12-30 | Novartis Ag | Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
CN111733186A (zh) * | 2020-07-03 | 2020-10-02 | 天津英科赛奥科技有限公司 | 靶向cd19的人源化嵌合抗原受体制备及其应用 |
EP4178678A1 (en) | 2020-07-07 | 2023-05-17 | Cancure, LLC | Mic antibodies and binding agents and methods of using the same |
CA3188656A1 (en) | 2020-07-17 | 2022-01-20 | Simurx, Inc. | Chimeric myd88 receptors for redirecting immunosuppressive signaling and related compositions and methods |
US20220031751A1 (en) | 2020-08-03 | 2022-02-03 | Kyverna Therapeutics, Inc. | Methods of producing t regulatory cells, methods of transducing t cells, and uses of the same |
US20230271940A1 (en) | 2020-08-03 | 2023-08-31 | Novartis Ag | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
WO2022029660A1 (en) | 2020-08-05 | 2022-02-10 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods |
CN116390946A (zh) | 2020-08-13 | 2023-07-04 | 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磷脂酰肌醇蛋白聚糖-1(gpc1)的含igg4铰链的嵌合抗原受体 |
AU2021329404A1 (en) | 2020-08-21 | 2023-04-20 | Novartis Ag | Compositions and methods for in vivo generation of car expressing cells |
CN114438034A (zh) * | 2020-11-06 | 2022-05-06 | 上海赛比曼生物科技有限公司 | 一种基因修饰的细胞制备方法 |
IL302412A (en) | 2020-11-06 | 2023-06-01 | Novartis Ag | Anti-CD19 and B-cell targeting agent combination therapy for the treatment of B-cell malignancies |
AU2021378316A1 (en) | 2020-11-13 | 2023-06-01 | Novartis Ag | Combination therapies with chimeric antigen receptor (car)-expressing cells |
US20230406922A1 (en) * | 2020-11-20 | 2023-12-21 | Simcere Zaiming Pharmaceutical Co., Ltd. | Humanized cd19 antibody and use thereof |
WO2022111562A1 (zh) * | 2020-11-26 | 2022-06-02 | 上海医药集团生物治疗技术有限公司 | 一种经修饰的免疫细胞及其应用 |
US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
WO2022133030A1 (en) | 2020-12-16 | 2022-06-23 | Juno Therapeutics, Inc. | Combination therapy of a cell therapy and a bcl2 inhibitor |
AR124414A1 (es) | 2020-12-18 | 2023-03-22 | Century Therapeutics Inc | Sistema de receptor de antígeno quimérico con especificidad de receptor adaptable |
CN117396607A (zh) | 2020-12-30 | 2024-01-12 | 阿劳诺斯治疗公司 | 包含多顺反子表达盒的重组载体及其使用方法 |
TW202242121A (zh) | 2021-01-11 | 2022-11-01 | 美商薩那生物科技公司 | 靶向cd8之病毒載體之用途 |
WO2022155375A2 (en) * | 2021-01-13 | 2022-07-21 | Washington University | MHC-INDEPENDENT TCRs AND METHODS OF MAKING AND USING SAME |
US20240115607A1 (en) | 2021-01-26 | 2024-04-11 | Cytocares (Shanghai) Inc. | Chimeric antigen receptor (car) constructs and nk cells expressing car constructs |
WO2022165419A1 (en) | 2021-02-01 | 2022-08-04 | Kyverna Therapeutics, Inc. | Methods for increasing t-cell function |
WO2022180586A1 (en) * | 2021-02-25 | 2022-09-01 | Senthil Natesan | Car t-cell product and method of preparation thereof |
US20240108654A1 (en) | 2021-03-03 | 2024-04-04 | Juno Therapeutics, Inc. | Combination of a t cell therapy and a dgk inhibitor |
AU2022241654A1 (en) | 2021-03-22 | 2023-09-28 | Juno Therapeutics, Inc. | 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 |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
IL307598A (en) | 2021-04-16 | 2023-12-01 | Juno Therapeutics Inc | T-cell therapy in patients who have had a previous stem cell transplant |
CA3214683A1 (en) | 2021-04-16 | 2022-10-20 | Julie Ann RYTLEWSKI | Combination therapies with bcma-directed t cell therapy |
AU2022267891A1 (en) | 2021-04-27 | 2023-11-09 | Novartis Ag | Viral vector production system |
WO2022234158A1 (es) * | 2021-05-06 | 2022-11-10 | Institut D'investigacions Biomèdiques August Pi I Sunyer (Idibaps) | Terapia de células t con receptor de antígeno quimérico específico de cd19 |
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 |
WO2022248602A1 (en) | 2021-05-25 | 2022-12-01 | Institut Curie | Myeloid cells overexpressing bcl2 |
AU2022288058A1 (en) | 2021-06-07 | 2023-11-16 | Agonox, Inc. | Cxcr5, pd-1, and icos expressing tumor reactive cd4 t cells and their use |
BR112023026141A2 (pt) | 2021-06-15 | 2024-03-05 | Takeda Pharmaceuticals Co | Métodos para produzir uma população de células enriquecida em células nk, para produzir células nk derivadas de células-tronco pluripotentes induzidas, para tratar um sujeito em necessidade de terapia de células e para produzir uma população de células compreendendo células progenitoras hematopoiéticas cd34+, e, populações de células nk e de células não classificadas |
CN113549600B (zh) * | 2021-06-30 | 2022-08-30 | 徐州医科大学 | 一种具有CD19的特异性抗性的CAR-iNKT细胞 |
EP4381081A1 (en) | 2021-08-04 | 2024-06-12 | Sana Biotechnology, Inc. | Use of cd4-targeted viral vectors |
EP4384621A1 (en) * | 2021-08-09 | 2024-06-19 | The Trustees of The University of Pennsylvania | Optimizing t cell differentiation state with micrornas |
EP4388000A1 (en) | 2021-08-20 | 2024-06-26 | Novartis AG | Methods of making chimeric antigen receptor?expressing cells |
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 |
KR20240099402A (ko) | 2021-11-09 | 2024-06-28 | 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 | 글리피칸-3(gpc3)을 표적으로 하는 igg4 힌지-포함 키메라 항원 수용체 및 이의 용도 |
TW202342757A (zh) | 2021-12-17 | 2023-11-01 | 美商薩那生物科技公司 | 經修飾副黏液病毒科附著醣蛋白 |
TW202342498A (zh) | 2021-12-17 | 2023-11-01 | 美商薩那生物科技公司 | 經修飾副黏液病毒科融合醣蛋白 |
WO2023150518A1 (en) | 2022-02-01 | 2023-08-10 | Sana Biotechnology, Inc. | Cd3-targeted lentiviral vectors and uses thereof |
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 |
WO2023156587A1 (en) | 2022-02-18 | 2023-08-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of tcr-deficient car-tregs in combination with anti-tcr complex monoclonal antibodies for inducing durable tolerance |
WO2023193015A1 (en) | 2022-04-01 | 2023-10-05 | Sana Biotechnology, Inc. | Cytokine receptor agonist and viral vector combination therapies |
WO2023208157A1 (zh) * | 2022-04-29 | 2023-11-02 | 上海先博生物科技有限公司 | 靶向cd19的嵌合抗原受体及其应用 |
WO2023215738A1 (en) | 2022-05-02 | 2023-11-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Compositions targeting gpc2 and gpc3 and their use for treating solid tumors |
WO2023213969A1 (en) | 2022-05-05 | 2023-11-09 | Juno Therapeutics Gmbh | Viral-binding protein and related reagents, articles, and methods of use |
WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
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 |
WO2023230548A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Method for predicting response to a t cell therapy |
WO2023230581A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Methods of manufacturing t cell therapies |
WO2023237663A1 (en) | 2022-06-09 | 2023-12-14 | Institut National de la Santé et de la Recherche Médicale | Use of the f359l missense irf4 variant for increasing the stability of regulatory t cells |
WO2023250400A1 (en) | 2022-06-22 | 2023-12-28 | Juno Therapeutics, Inc. | Treatment methods for second line therapy of cd19-targeted car t cells |
WO2024015995A2 (en) * | 2022-07-15 | 2024-01-18 | Albert Einstein College Of Medicine | Chimeric antigen receptors comprising a tmigd2 costimulatory domain and associated methods of using the same |
WO2024047110A1 (en) | 2022-08-31 | 2024-03-07 | Institut National de la Santé et de la Recherche Médicale | Method to generate more efficient car-t cells |
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 |
WO2024074713A1 (en) | 2022-10-07 | 2024-04-11 | Institut National de la Santé et de la Recherche Médicale | Method to generate improving car-t cells |
WO2024081820A1 (en) | 2022-10-13 | 2024-04-18 | Sana Biotechnology, Inc. | Viral particles targeting hematopoietic stem cells |
WO2024086191A2 (en) * | 2022-10-18 | 2024-04-25 | Kite Pharma, Inc. | Car-t constructs comprising a novel cd19 binder combined with il18 and methods of using the same |
WO2024089639A1 (en) | 2022-10-26 | 2024-05-02 | Novartis Ag | Lentiviral formulations |
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 |
CN116063575A (zh) * | 2022-11-15 | 2023-05-05 | 北京瑜阳科技有限公司 | 一种嵌合抗原受体(car)以及在治疗肿瘤中的应用 |
WO2024124132A1 (en) | 2022-12-09 | 2024-06-13 | Juno Therapeutics, Inc. | Machine learning methods for predicting cell phenotype using holographic imaging |
WO2024133052A1 (en) * | 2022-12-19 | 2024-06-27 | Universität Basel Vizerektorat Forschung | T-cell receptor fusion protein |
Family Cites Families (234)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3381783D1 (de) | 1982-03-03 | 1990-09-13 | Genentech Inc | Menschliches antithrombin iii, dns sequenzen dafuer, expressions- und klonierungsvektoren die solche sequenzen enthalten und damit transformierte zellkulturen, verfahren zur expression von menschlichem antithrombin iii und diese enthaltende pharmazeutische zusammensetzungen. |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4882282A (en) | 1985-08-16 | 1989-11-21 | Immunex Corporation | DNA sequences encoding bovine interleukin-2 |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5906936A (en) | 1988-05-04 | 1999-05-25 | Yeda Research And Development Co. Ltd. | Endowing lymphocytes with antibody specificity |
US6303121B1 (en) | 1992-07-30 | 2001-10-16 | Advanced Research And Technology | Method of using human receptor protein 4-1BB |
US5858358A (en) | 1992-04-07 | 1999-01-12 | The United States Of America As Represented By The Secretary Of The Navy | Methods for selectively stimulating proliferation of T cells |
US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
DE69123241T2 (de) | 1990-12-14 | 1997-04-17 | Cell Genesys Inc | Chimärische ketten zur transduktion von rezeptorverbundenen signalwegen |
US6319494B1 (en) | 1990-12-14 | 2001-11-20 | Cell Genesys, Inc. | Chimeric chains for receptor-associated signal transduction pathways |
US7049136B2 (en) | 1991-03-07 | 2006-05-23 | The General Hospital Corporation | Redirection of cellular immunity by receptor chimeras |
IL101147A (en) | 1991-03-07 | 2004-06-20 | Gen Hospital Corp | Change of direction of cellular immunity by chimera receptors |
US6004811A (en) | 1991-03-07 | 1999-12-21 | The Massachussetts General Hospital | Redirection of cellular immunity by protein tyrosine kinase chimeras |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
GB9125768D0 (en) | 1991-12-04 | 1992-02-05 | Hale Geoffrey | Therapeutic method |
JP4157160B2 (ja) | 1991-12-13 | 2008-09-24 | ゾーマ テクノロジー リミテッド | 改変抗体可変領域の調製のための方法 |
GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
IL104570A0 (en) | 1992-03-18 | 1993-05-13 | Yeda Res & Dev | Chimeric genes and cells transformed therewith |
US8211422B2 (en) | 1992-03-18 | 2012-07-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric receptor genes and cells transformed therewith |
US5350674A (en) | 1992-09-04 | 1994-09-27 | Becton, Dickinson And Company | Intrinsic factor - horse peroxidase conjugates and a method for increasing the stability thereof |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
US7211259B1 (en) | 1993-05-07 | 2007-05-01 | Immunex Corporation | 4-1BB polypeptides and DNA encoding 4-1BB polypeptides |
AU697482B2 (en) | 1993-09-16 | 1998-10-08 | Indiana University Research And Technology Corporation | Human receptor H4-1BB |
DK0758394T3 (da) | 1994-05-02 | 2003-03-03 | Bernd Groner | Bifunktionelt protein, fremstilling og anvendelse |
US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
US5786464C1 (en) | 1994-09-19 | 2012-04-24 | Gen Hospital Corp | Overexpression of mammalian and viral proteins |
US5712149A (en) | 1995-02-03 | 1998-01-27 | Cell Genesys, Inc. | Chimeric receptor molecules for delivery of co-stimulatory signals |
US6103521A (en) | 1995-02-06 | 2000-08-15 | Cell Genesys, Inc. | Multispecific chimeric receptors |
DE69634855T2 (de) | 1995-02-24 | 2006-05-18 | The General Hospital Corp., Boston | Neuorientierung der zellulären immunität durch rezeptorchimären |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US6692964B1 (en) | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
GB9526131D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Recombinant chimeric receptors |
US5874240A (en) | 1996-03-15 | 1999-02-23 | Human Genome Sciences, Inc. | Human 4-1BB receptor splicing variant |
US6111090A (en) | 1996-08-16 | 2000-08-29 | Schering Corporation | Mammalian cell surface antigens; related reagents |
AU4055697A (en) | 1996-08-16 | 1998-03-06 | Schering Corporation | Mammalian cell surface antigens; related reagents |
US6114148C1 (en) | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
AU744160B2 (en) | 1996-10-25 | 2002-02-14 | Cell Genesys, Inc. | Targeted cytolysis of cancer cells |
US20030060444A1 (en) | 1997-06-25 | 2003-03-27 | Celltech Therapeutics, Ltd. | Cell activation process and reagents therefor |
GB9713473D0 (en) | 1997-06-25 | 1997-09-03 | Celltech Therapeutics Ltd | Biological products |
EP1017716A4 (en) | 1997-09-19 | 2001-01-03 | Gen Hospital Corp | CAR RECEPTORS, MOLECULES AND RELATED METHODS |
EP1025228A4 (en) | 1997-10-21 | 2002-09-18 | Human Genome Sciences Inc | HUMAN PROTEIN TR11, TR11SV1 AND TR11SV2 SIMILAR TO THE TUMOR NECROSIS FACTOR RECEPTOR |
WO1999021581A1 (en) | 1997-10-28 | 1999-05-06 | Steeves John D | Immunological compositions and methods of use to transiently alter mammalian central nervous system myelin to promote neuronal regeneration |
CA2319236A1 (en) | 1998-02-09 | 1999-08-12 | Genentech, Inc. | Novel tumor necrosis factor receptor homolog and nucleic acids encoding the same |
ATE298248T1 (de) | 1998-04-15 | 2005-07-15 | Brigham & Womens Hospital | T-zell inhibierende rezeptorzusammensetzungen sowie deren verwendung |
GB9809658D0 (en) | 1998-05-06 | 1998-07-01 | Celltech Therapeutics Ltd | Biological products |
EP1109921A4 (en) | 1998-09-04 | 2002-08-28 | Sloan Kettering Inst Cancer | FOR PROSTATE-SPECIFIC MEMBRANE-ANTI-SPECIFIC FUSION RECEPTORS AND THEIR USE |
WO2000023573A2 (en) | 1998-10-20 | 2000-04-27 | City Of Hope | Cd20-specific redirected t cells and their use in cellular immunotherapy of cd20+ malignancies |
US7052906B1 (en) | 1999-04-16 | 2006-05-30 | Celltech R & D Limited | Synthetic transmembrane components |
WO2001003720A2 (en) | 1999-07-12 | 2001-01-18 | Genentech, Inc. | Promotion or inhibition of angiogenesis and cardiovascularization by tumor necrosis factor ligand/receptor homologs |
AU1086501A (en) | 1999-10-15 | 2001-04-30 | Carnegie Institution Of Washington | Rna interference pathway genes as tools for targeted genetic interference |
GB9925848D0 (en) | 1999-11-01 | 1999-12-29 | Celltech Therapeutics Ltd | Biological products |
US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
CA2391129A1 (en) | 1999-11-10 | 2001-05-17 | The Uab Research Foundation | Lentiviral vector transduction of hematopoietic stem cells |
US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
DK1257632T3 (da) | 2000-02-24 | 2008-01-28 | Xcyte Therapies Inc | Samtidig stimulering og opkoncentrering af celler |
US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
IL136511A0 (en) | 2000-06-01 | 2001-06-14 | Gavish Galilee Bio Appl Ltd | Genetically engineered mhc molecules |
AU2001275474A1 (en) | 2000-06-12 | 2001-12-24 | Akkadix Corporation | Materials and methods for the control of nematodes |
GB0025307D0 (en) | 2000-10-16 | 2000-11-29 | Celltech Chiroscience Ltd | Biological products |
CA2425862C (en) * | 2000-11-07 | 2013-01-22 | City Of Hope | Cd19-specific redirected immune cells |
US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
CN1294148C (zh) | 2001-04-11 | 2007-01-10 | 中国科学院遗传与发育生物学研究所 | 环状单链三特异抗体 |
US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
US7514537B2 (en) | 2001-04-30 | 2009-04-07 | City Of Hope | Chimeric immunoreceptor useful in treating human gliomas |
US20030171546A1 (en) | 2001-04-30 | 2003-09-11 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
US20030148982A1 (en) | 2001-11-13 | 2003-08-07 | Brenner Malcolm K. | Bi-spcific chimeric T cells |
US7745140B2 (en) | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
US7638326B2 (en) | 2002-01-03 | 2009-12-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform |
US7638325B2 (en) | 2002-01-03 | 2009-12-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform |
CA2472341C (en) | 2002-02-01 | 2011-06-21 | Ariad Gene Therapeutics, Inc. | Phosphorus-containing compounds & uses thereof |
US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
DE60305919T2 (de) | 2002-06-28 | 2007-01-18 | Domantis Limited, Cambridge | Dual-specifische liganden mit erhöhter halbwertszeit |
ES2367430T3 (es) | 2002-12-23 | 2011-11-03 | Wyeth Llc | Anticuerpos contra pd-1 y sus usos. |
US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
US7402431B2 (en) | 2004-03-01 | 2008-07-22 | Immunovative Therapies, Ltd. | T-cell therapy formulation |
JP4638876B2 (ja) | 2003-05-23 | 2011-02-23 | ワイス | Gitrリガンド及びgitrリガンド関連分子及び抗体及びその使用 |
EP1638510B1 (en) | 2003-07-01 | 2015-09-02 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
EP1660126A1 (en) | 2003-07-11 | 2006-05-31 | Schering Corporation | Agonists or antagonists of the clucocorticoid-induced tumour necrosis factor receptor (gitr) or its ligand for the treatment of immune disorders, infections and cancer |
CA2536238C (en) | 2003-08-18 | 2015-04-07 | Medimmune, Inc. | Humanization of antibodies |
WO2005019429A2 (en) | 2003-08-22 | 2005-03-03 | Potentia Pharmaceuticals, Inc. | Compositions and methods for enhancing phagocytosis or phagocyte activity |
US20050042664A1 (en) | 2003-08-22 | 2005-02-24 | Medimmune, Inc. | Humanization of antibodies |
US20050113564A1 (en) | 2003-11-05 | 2005-05-26 | St. Jude Children's Research Hospital | Chimeric receptors with 4-1BB stimulatory signaling domain |
US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
JP2007518399A (ja) | 2003-12-02 | 2007-07-12 | ジェンザイム コーポレイション | 肺癌を診断および治療する組成物並びに方法 |
GB0409799D0 (en) | 2004-04-30 | 2004-06-09 | Isis Innovation | Method of generating improved immune response |
JP5070045B2 (ja) | 2004-05-27 | 2012-11-07 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 新規人工抗原提示細胞およびそれらの用途 |
WO2006083289A2 (en) | 2004-06-04 | 2006-08-10 | Duke University | Methods and compositions for enhancement of immunity by in vivo depletion of immunosuppressive cell activity |
JP2008512352A (ja) | 2004-07-17 | 2008-04-24 | イムクローン システムズ インコーポレイティド | 新規な四価の二重特異性抗体 |
WO2006036445A2 (en) | 2004-09-24 | 2006-04-06 | Trustees Of Dartmouth College | Chimeric nk receptor and methods for treating cancer |
US7462697B2 (en) | 2004-11-08 | 2008-12-09 | Epitomics, Inc. | Methods for antibody engineering |
EP3530321A1 (en) | 2004-12-10 | 2019-08-28 | Peter MacCallum Cancer Institute | Methods and compositions for adoptive immunotherapy |
PT1866339E (pt) | 2005-03-25 | 2013-09-03 | Gitr Inc | Moléculas de ligação a gitr e suas utilizações |
CN101213297B (zh) | 2005-05-09 | 2013-02-13 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及单独使用或与其它免疫治疗剂联合使用抗pd-1抗体来治疗癌症的方法 |
MX2007014474A (es) | 2005-05-17 | 2008-02-07 | Univ Connecticut | Composiciones y metodos para inmunomodulacion en un organismo. |
KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
US20070036773A1 (en) | 2005-08-09 | 2007-02-15 | City Of Hope | Generation and application of universal T cells for B-ALL |
BRPI0615026A8 (pt) | 2005-08-19 | 2018-03-06 | Abbott Lab | imunoglobulina de domínio variável duplo e seus usos |
NZ596494A (en) | 2006-01-13 | 2013-07-26 | Us Gov Nat Inst Health | Codon optimized il-15 and il-15r-alpha genes for expression in mammalian cells |
EP1981969A4 (en) | 2006-01-19 | 2009-06-03 | Genzyme Corp | ANTI-GITRANT ANTIBODIES FOR THE TREATMENT OF CANCER |
CN102887900B (zh) | 2006-09-22 | 2015-04-29 | 药品循环公司 | 布鲁顿酪氨酸激酶的抑制剂 |
US20100105136A1 (en) | 2006-10-09 | 2010-04-29 | The General Hospital Corporation | Chimeric t-cell receptors and t-cells targeting egfrviii on tumors |
US9382327B2 (en) * | 2006-10-10 | 2016-07-05 | Vaccinex, Inc. | Anti-CD20 antibodies and methods of use |
EP1916259A1 (en) | 2006-10-26 | 2008-04-30 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Anti-glycoprotein VI SCFV fragment for treatment of thrombosis |
US20080131415A1 (en) | 2006-11-30 | 2008-06-05 | Riddell Stanley R | Adoptive transfer of cd8 + t cell clones derived from central memory cells |
CA2584494A1 (en) | 2007-03-27 | 2008-09-27 | Jeffrey A. Medin | Vector encoding therapeutic polypeptide and safety elements to clear transduced cells |
EP3357338A1 (en) | 2007-03-30 | 2018-08-08 | Memorial Sloan-Kettering Cancer Center | Constitutive expression of costimulatory ligands on adoptively transferred t lymphocytes |
KR101586617B1 (ko) | 2007-06-18 | 2016-01-20 | 머크 샤프 앤 도메 비.브이. | 사람 프로그램된 사멸 수용체 pd-1에 대한 항체 |
ES2466916T3 (es) | 2007-06-27 | 2014-06-11 | Admune Therapeutics Llc | Complejos de IL-15 e IL-15R alfa y usos de los mismos |
JP5932217B2 (ja) | 2007-07-12 | 2016-06-08 | ジーアイティーアール, インコーポレイテッド | Gitr結合分子を使用する併用療法 |
KR101658083B1 (ko) * | 2007-10-19 | 2016-09-30 | 시애틀 지네틱스, 인크. | 씨디19 결합제 및 그의 용도 |
CA2703947C (en) | 2007-10-26 | 2018-12-04 | Governing Council Of The University Of Toronto | Therapeutic and diagnostic methods using tim-3 |
WO2009091826A2 (en) * | 2008-01-14 | 2009-07-23 | The Board Of Regents Of The University Of Texas System | Compositions and methods related to a human cd19-specific chimeric antigen receptor (h-car) |
WO2009097140A1 (en) | 2008-01-30 | 2009-08-06 | Memorial Sloan-Kettering Cancer Center | Methods for off -the -shelf tumor immunotherapy using allogeneic t-cell precursors |
HUE034465T2 (en) | 2008-02-11 | 2018-02-28 | Cure Tech Ltd | Monoclonal antibodies for tumor treatment |
US8379824B2 (en) | 2008-03-06 | 2013-02-19 | At&T Intellectual Property I, Lp | Methods and apparatus to provide a network-based caller identification service in a voice over internet protocol network |
EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
KR20110044992A (ko) | 2008-07-02 | 2011-05-03 | 이머전트 프로덕트 디벨롭먼트 시애틀, 엘엘씨 | TGF-β 길항제 다중-표적 결합 단백질 |
AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
NZ591130A (en) | 2008-08-25 | 2012-09-28 | Amplimmune Inc | Compositions comprising a PD-1 antagonists and cyclophosphamide and methods of use thereof |
EP2331566B1 (en) * | 2008-08-26 | 2015-10-07 | City of Hope | Method and compositions for enhanced anti-tumor effector functioning of t cells |
WO2010030002A1 (ja) | 2008-09-12 | 2010-03-18 | 国立大学法人三重大学 | 外来性gitrリガンド発現細胞 |
PE20120341A1 (es) | 2008-12-09 | 2012-04-24 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t |
US9206440B2 (en) | 2009-01-23 | 2015-12-08 | Roger Williams Hospital | Viral vectors encoding multiple highly homologus non-viral polypeptides and the use of same |
TW201031421A (en) * | 2009-01-29 | 2010-09-01 | Abbott Lab | IL-1 binding proteins |
EP3192811A1 (en) | 2009-02-09 | 2017-07-19 | Université d'Aix-Marseille | Pd-1 antibodies and pd-l1 antibodies and uses thereof |
CN102421800A (zh) * | 2009-02-23 | 2012-04-18 | 格兰马克药品股份有限公司 | 结合cd19的人源化抗体及其用途 |
JP2013501817A (ja) | 2009-08-14 | 2013-01-17 | アメリカ合衆国 | 胸腺産出の増大およびリンパ球減少症の治療のためのil−15の使用 |
WO2011028683A1 (en) | 2009-09-03 | 2011-03-10 | Schering Corporation | Anti-gitr antibodies |
JP5934099B2 (ja) | 2009-10-01 | 2016-06-15 | アメリカ合衆国 | 抗血管内皮増殖因子受容体−2キメラ抗原受容体及び癌の治療のためのその使用 |
WO2011059836A2 (en) | 2009-10-29 | 2011-05-19 | Trustees Of Dartmouth College | T cell receptor-deficient t cell compositions |
GB0919054D0 (en) | 2009-10-30 | 2009-12-16 | Isis Innovation | Treatment of obesity |
WO2011066342A2 (en) | 2009-11-24 | 2011-06-03 | Amplimmune, Inc. | Simultaneous inhibition of pd-l1/pd-l2 |
ME02505B (me) | 2009-12-29 | 2017-02-20 | Aptevo Res & Development Llc | Heterodimerni vezujući proteini i njihove upotrebe |
WO2011097477A1 (en) | 2010-02-04 | 2011-08-11 | The Trustees Of The University Of Pennsylvania | Icos critically regulates the expansion and function of inflammatory human th17 cells |
WO2012050374A2 (en) * | 2010-10-13 | 2012-04-19 | Innocell, Inc. | Immunotherapy for solid tumors |
CA2816379A1 (en) | 2010-10-27 | 2012-05-03 | Baylor College Of Medicine | Chimeric cd27 receptors for redirecting t cells to cd70-positive malignancies |
BR122021026169B1 (pt) | 2010-12-09 | 2023-12-12 | The Trustees Of The University Of Pennsylvania | Uso de uma célula |
CA3102782A1 (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 |
AU2012207356A1 (en) | 2011-01-18 | 2013-08-01 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treating cancer |
AU2012230780B2 (en) | 2011-03-23 | 2016-10-27 | Fred Hutchinson Cancer Center | Method and compositions for cellular immunotherapy |
WO2012127464A2 (en) | 2011-03-23 | 2012-09-27 | Gavish-Galilee Bio Applications Ltd | Constitutively activated t cells for use in adoptive cell therapy |
AU2012236068A1 (en) | 2011-04-01 | 2013-10-17 | Eureka Therapeutics, Inc. | T cell receptor-like antibodies specific for a WT1 peptide presented by HLA-A2 |
IL285335B2 (en) | 2011-04-08 | 2023-12-01 | Us Health | Chimeric antigen receptors against epidermal growth factor receptor variant III and their use in cancer treatment |
CN107164330A (zh) | 2011-04-08 | 2017-09-15 | 贝勒医学院 | 使用嵌合细胞因子受体逆转肿瘤微环境的影响 |
US20130071414A1 (en) | 2011-04-27 | 2013-03-21 | Gianpietro Dotti | Engineered cd19-specific t lymphocytes that coexpress il-15 and an inducible caspase-9 based suicide gene for the treatment of b-cell malignancies |
WO2013016352A1 (en) | 2011-07-25 | 2013-01-31 | Nationwide Children's Hospital, Inc. | Recombinant virus products and methods for inhibition of expression of dux4 |
EP2736540B1 (en) | 2011-07-29 | 2019-03-13 | The Trustees Of The University Of Pennsylvania | Switch costimulatory receptors |
WO2013033626A2 (en) | 2011-08-31 | 2013-03-07 | Trustees Of Dartmouth College | Nkp30 receptor targeted therapeutics |
US20130108641A1 (en) | 2011-09-14 | 2013-05-02 | Sanofi | Anti-gitr antibodies |
EP2755487B1 (en) | 2011-09-16 | 2018-12-19 | Baylor College Of Medicine | Targeting the tumor microenvironment using manipulated nkt cells |
KR20140060541A (ko) | 2011-09-16 | 2014-05-20 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 암을 치료하기 위한 rna 조작된 t 세포 |
IN2014CN02906A (da) | 2011-10-20 | 2015-07-03 | Us Health | |
EA201491572A1 (ru) | 2012-02-22 | 2014-12-30 | Дзе Трастиз Оф Дзе Юниверсити Оф Пенсильвания | Композиции и способы получения устойчивой популяции t-клеток, используемых для лечения злокачественного новообразования |
US9714278B2 (en) | 2012-02-22 | 2017-07-25 | The Trustees Of The University Of Pennsylvania | Use of ICOS-based CARs to enhance antitumor activity and CAR persistence |
CN104136458A (zh) | 2012-02-22 | 2014-11-05 | 宾夕法尼亚大学董事会 | 在第二代嵌合抗原受体中cd2信号传导结构域的使用 |
BR112015000657B1 (pt) | 2012-07-13 | 2023-12-05 | The Trustees Of The University Of Pennsylvania | Uso de uma célula geneticamente modificada para expressar um car |
US20160235787A1 (en) | 2012-07-13 | 2016-08-18 | The Trustees Of The University Of Pennsylvania | Epitope Spreading Associated with CAR T-Cells |
KR20150029714A (ko) | 2012-07-13 | 2015-03-18 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 이중특이적 항체의 공-도입에 의한 car 세포의 활성 증강 |
JP6482461B2 (ja) | 2012-07-13 | 2019-03-13 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 投与に関する形質導入t細胞の適合性の評価方法 |
WO2014011984A1 (en) | 2012-07-13 | 2014-01-16 | The Trustees Of The University Of Pennsylvania | Toxicity management for anti-tumor activity of cars |
IN2014DN10889A (da) | 2012-07-13 | 2015-09-11 | Univ Pennsylvania | |
RS61345B1 (sr) | 2012-08-20 | 2021-02-26 | Hutchinson Fred Cancer Res | Postupak i kompozicije za ćelijsku imunoterapiju |
US9937205B2 (en) | 2012-09-04 | 2018-04-10 | The Trustees Of The University Of Pennsylvania | Inhibition of diacylglycerol kinase to augment adoptive T cell transfer |
AR092745A1 (es) | 2012-10-01 | 2015-04-29 | Univ Pennsylvania | Composiciones que comprenden un dominio de union anti-fap y metodos para hacer blanco en celulas estromales para el tratamiento del cancer |
WO2014055657A1 (en) | 2012-10-05 | 2014-04-10 | The Trustees Of The University Of Pennsylvania | Use of a trans-signaling approach in chimeric antigen receptors |
WO2014130635A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
RU2708032C2 (ru) | 2013-02-20 | 2019-12-03 | Новартис Аг | ЛЕЧЕНИЕ РАКА С ИСПОЛЬЗОВАНИЕМ ХИМЕРНОГО АНТИГЕНСПЕЦИФИЧЕСКОГО РЕЦЕПТОРА НА ОСНОВЕ ГУМАНИЗИРОВАННОГО АНТИТЕЛА ПРОТИВ EGFRvIII |
EP2970426B1 (en) | 2013-03-15 | 2019-08-28 | Michael C. Milone | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
CA2926698C (en) | 2013-10-15 | 2021-06-22 | The California Institute For Biomedical Research | Chimeric antigen receptor t cell switches and uses thereof |
US9512084B2 (en) | 2013-11-29 | 2016-12-06 | Novartis Ag | Amino pyrimidine derivatives |
ES2811923T3 (es) | 2013-12-17 | 2021-03-15 | Genentech Inc | Anticuerpos anti-CD3 y métodos de uso |
CA3225453A1 (en) | 2013-12-19 | 2015-06-25 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
EP3087101B1 (en) | 2013-12-20 | 2024-06-05 | Novartis AG | Regulatable chimeric antigen receptor |
WO2015112626A1 (en) | 2014-01-21 | 2015-07-30 | June Carl H | Enhanced antigen presenting ability of car t cells by co-introduction of costimulatory molecules |
EP3811970A1 (en) | 2014-03-15 | 2021-04-28 | Novartis AG | Regulatable chimeric antigen receptor |
JP2017513818A (ja) | 2014-03-15 | 2017-06-01 | ノバルティス アーゲー | キメラ抗原受容体を使用する癌の処置 |
DK3119397T3 (da) | 2014-03-19 | 2022-03-28 | Infinity Pharmaceuticals Inc | Heterocykliske forbindelser til anvendelse i behandling af PI3K-gamma-medierede lidelser |
HUE054588T2 (hu) | 2014-04-07 | 2021-09-28 | Novartis Ag | Rák kezelése CD19 elleni, kiméra antigénreceptor alkalmazásával |
CA2955154C (en) | 2014-07-21 | 2023-10-31 | Novartis Ag | Treatment of cancer using a cd33 chimeric antigen receptor |
US20170274014A1 (en) | 2014-07-21 | 2017-09-28 | Jennifer Brogdon | Combinations of low, immune enhancing, doses of mtor inhibitors and cars |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
MY181834A (en) | 2014-07-21 | 2021-01-08 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
AR101829A1 (es) | 2014-07-21 | 2017-01-18 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno cll-1 |
EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
WO2016014501A1 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Sortase molecules and uses thereof |
EP4205749A1 (en) | 2014-07-31 | 2023-07-05 | Novartis AG | Subset-optimized chimeric antigen receptor-containing cells |
CA2958200A1 (en) | 2014-08-14 | 2016-02-18 | Novartis Ag | Treatment of cancer using a gfr alpha-4 chimeric antigen receptor |
PL3183268T3 (pl) | 2014-08-19 | 2020-09-07 | Novartis Ag | Chimeryczny receptor antygenowy (CAR) anty-CD123 do zastosowania w leczeniu nowotworu złośliwego |
WO2016044605A1 (en) | 2014-09-17 | 2016-03-24 | Beatty, Gregory | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
KR20170068504A (ko) | 2014-10-08 | 2017-06-19 | 노파르티스 아게 | 키메라 항원 수용체 요법에 대한 치료 반응성을 예측하는 바이오마커 및 그의 용도 |
WO2016061368A1 (en) | 2014-10-15 | 2016-04-21 | The Children's Hospital Of Philadelphia | Compositions and methods for treating b-lymphoid malignancies |
IL253149B2 (en) | 2014-12-29 | 2023-11-01 | Novartis Ag | Methods for preparing cells expressing a chimeric receptor antigen |
WO2016115482A1 (en) | 2015-01-16 | 2016-07-21 | Novartis Pharma Ag | Phosphoglycerate kinase 1 (pgk) promoters and methods of use for expressing chimeric antigen receptor |
WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
ES2876974T3 (es) | 2015-04-07 | 2021-11-15 | Novartis Ag | Combinación de terapia con receptor de antígeno quimérico y derivados de amino pirimidina |
EP4056588A1 (en) | 2015-04-08 | 2022-09-14 | Novartis AG | Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car)- expressing cell |
CA2982996A1 (en) | 2015-04-17 | 2016-10-20 | David Maxwell Barrett | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
EP3286211A1 (en) | 2015-04-23 | 2018-02-28 | Novartis AG | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
AU2016297014B2 (en) | 2015-07-21 | 2021-06-17 | Novartis Ag | Methods for improving the efficacy and expansion of immune cells |
WO2017027392A1 (en) | 2015-08-07 | 2017-02-16 | Novartis Ag | Treatment of cancer using chimeric cd3 receptor proteins |
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 |
MX2018003353A (es) | 2015-09-17 | 2018-09-17 | Novartis Ag | Terapias con celulas cart con una eficacia mejorada. |
JP7082055B2 (ja) | 2015-12-22 | 2022-06-07 | ノバルティス アーゲー | 抗癌治療における組み合わせ使用のためのメソテリンキメラ抗原受容体(car)およびpd-l1阻害剤に対する抗体 |
CN109072195A (zh) | 2015-12-30 | 2018-12-21 | 诺华股份有限公司 | 具有增强功效的免疫效应细胞疗法 |
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 |
CN118021943A (zh) | 2016-07-28 | 2024-05-14 | 诺华股份有限公司 | 嵌合抗原受体和pd-1抑制剂的组合疗法 |
EP3490590A2 (en) | 2016-08-01 | 2019-06-05 | Novartis AG | Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule |
US20190298715A1 (en) | 2016-09-30 | 2019-10-03 | Novartis Ag | Immune effector cell therapies with enhanced efficacy |
CN117866991A (zh) | 2016-10-07 | 2024-04-12 | 诺华股份有限公司 | 用于治疗癌症的嵌合抗原受体 |
EP4043485A1 (en) | 2017-01-26 | 2022-08-17 | Novartis AG | Cd28 compositions and methods for chimeric antigen receptor therapy |
JP2020506700A (ja) | 2017-01-31 | 2020-03-05 | ノバルティス アーゲー | 多重特異性を有するキメラt細胞受容体タンパク質を用いた癌の治療 |
WO2018160731A1 (en) | 2017-02-28 | 2018-09-07 | Novartis Ag | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
BR112019019426A2 (pt) | 2017-03-22 | 2020-05-26 | Novartis Ag | Biomarcadores e terapias com células t car com eficácia intensificada |
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 |
US20200061113A1 (en) | 2018-04-12 | 2020-02-27 | Novartis Ag | Chimeric antigen receptor therapy characterization assays and uses thereof |
US20200085869A1 (en) | 2018-05-16 | 2020-03-19 | Novartis Ag | Therapeutic regimens for chimeric antigen receptor therapies |
AU2019284911A1 (en) | 2018-06-13 | 2020-12-17 | Novartis Ag | BCMA chimeric antigen receptors and uses thereof |
-
2014
- 2014-03-14 UY UY0001035468A patent/UY35468A/es not_active Application Discontinuation
- 2014-03-14 TW TW103109821A patent/TWI654206B/zh active
- 2014-03-15 HR HRP20220767TT patent/HRP20220767T1/hr unknown
- 2014-03-15 MX MX2015013194A patent/MX2015013194A/es active IP Right Grant
- 2014-03-15 RU RU2020100865A patent/RU2020100865A/ru unknown
- 2014-03-15 CN CN201480027401.4A patent/CN105392888B/zh active Active
- 2014-03-15 ES ES19158368T patent/ES2923397T3/es active Active
- 2014-03-15 WO PCT/US2014/029943 patent/WO2014153270A1/en active Application Filing
- 2014-03-15 EP EP19158368.1A patent/EP3539986B1/en active Active
- 2014-03-15 PT PT191583681T patent/PT3539986T/pt unknown
- 2014-03-15 SG SG11201506603PA patent/SG11201506603PA/en unknown
- 2014-03-15 HU HUE19158368A patent/HUE058832T2/hu unknown
- 2014-03-15 US US14/214,728 patent/US10221245B2/en active Active
- 2014-03-15 HU HUE14722469A patent/HUE042803T2/hu unknown
- 2014-03-15 PL PL19158368.1T patent/PL3539986T3/pl unknown
- 2014-03-15 RU RU2015144332A patent/RU2711975C2/ru active
- 2014-03-15 DK DK14722469.5T patent/DK2970482T3/da active
- 2014-03-15 LT LTEP14722469.5T patent/LT2970482T/lt unknown
- 2014-03-15 EP EP14722469.5A patent/EP2970482B1/en active Active
- 2014-03-15 CN CN202210634273.6A patent/CN115287292A/zh active Pending
- 2014-03-15 EP EP22159001.1A patent/EP4067382A1/en active Pending
- 2014-03-15 CA CA2907100A patent/CA2907100C/en active Active
- 2014-03-15 AU AU2014236098A patent/AU2014236098B8/en active Active
- 2014-03-15 BR BR112015021819A patent/BR112015021819A2/pt not_active Application Discontinuation
- 2014-03-15 SI SI201431971T patent/SI3539986T1/sl unknown
- 2014-03-15 KR KR1020157029649A patent/KR102293062B1/ko active IP Right Grant
- 2014-03-15 JP JP2016503288A patent/JP6466401B2/ja active Active
- 2014-03-15 ES ES14722469T patent/ES2734549T3/es active Active
- 2014-03-15 PT PT14722469T patent/PT2970482T/pt unknown
- 2014-03-15 DK DK19158368.1T patent/DK3539986T3/da active
- 2014-03-15 MY MYPI2015702773A patent/MY187624A/en unknown
- 2014-03-15 PL PL14722469T patent/PL2970482T3/pl unknown
- 2014-03-15 SG SG10201806293WA patent/SG10201806293WA/en unknown
- 2014-03-15 LT LTEP19158368.1T patent/LT3539986T/lt unknown
-
2015
- 2015-09-07 IL IL241261A patent/IL241261B/en active IP Right Grant
- 2015-09-15 MX MX2020007021A patent/MX2020007021A/es unknown
-
2016
- 2016-06-14 HK HK16106845.6A patent/HK1218922A1/zh unknown
-
2018
- 2018-11-15 US US16/192,375 patent/US10927184B2/en active Active
-
2019
- 2019-01-09 JP JP2019001925A patent/JP7187327B2/ja active Active
- 2019-08-15 AU AU2019216689A patent/AU2019216689C1/en active Active
-
2020
- 2020-12-23 US US17/132,674 patent/US20210284752A1/en active Pending
-
2021
- 2021-02-22 JP JP2021026430A patent/JP7439002B2/ja active Active
-
2022
- 2022-03-23 AU AU2022202024A patent/AU2022202024A1/en active Pending
-
2024
- 2024-02-14 JP JP2024020429A patent/JP2024056877A/ja active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2019216689C1 (en) | Treatment of cancer using humanized anti-CD19 chimeric antigen receptor | |
US11028177B2 (en) | Effective targeting of primary human leukemia using anti-CD123 chimeric antigen receptor engineered T cells | |
US20210347851A1 (en) | Cd19 chimeric antigen receptor (car) and cd22 car combination therapies | |
US20220047633A1 (en) | Cd22 chimeric antigen receptor (car) therapies |