WO2017120998A1 - Composition thérapeutique pour traiter un glioblastome - Google Patents
Composition thérapeutique pour traiter un glioblastome Download PDFInfo
- Publication number
- WO2017120998A1 WO2017120998A1 PCT/CN2016/073482 CN2016073482W WO2017120998A1 WO 2017120998 A1 WO2017120998 A1 WO 2017120998A1 CN 2016073482 W CN2016073482 W CN 2016073482W WO 2017120998 A1 WO2017120998 A1 WO 2017120998A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lymphocyte
- lymphocytes
- nucleic acid
- acid molecule
- transgenic
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title claims abstract description 34
- 208000005017 glioblastoma Diseases 0.000 title claims description 32
- 210000004698 lymphocyte Anatomy 0.000 claims abstract description 269
- 210000004027 cell Anatomy 0.000 claims abstract description 135
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 128
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 122
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 112
- 230000009261 transgenic effect Effects 0.000 claims abstract description 101
- 108010087914 epidermal growth factor receptor VIII Proteins 0.000 claims abstract description 83
- 230000003834 intracellular effect Effects 0.000 claims abstract description 75
- 238000000034 method Methods 0.000 claims abstract description 58
- 239000000427 antigen Substances 0.000 claims abstract description 49
- 108091007433 antigens Proteins 0.000 claims abstract description 49
- 102000036639 antigens Human genes 0.000 claims abstract description 49
- 201000011510 cancer Diseases 0.000 claims abstract description 35
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims abstract description 14
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims abstract description 14
- 210000000170 cell membrane Anatomy 0.000 claims abstract description 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims abstract 12
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims abstract 12
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims abstract 12
- 239000004055 small Interfering RNA Substances 0.000 claims description 101
- 150000007523 nucleic acids Chemical class 0.000 claims description 99
- 102000039446 nucleic acids Human genes 0.000 claims description 98
- 108020004707 nucleic acids Proteins 0.000 claims description 98
- 230000002147 killing effect Effects 0.000 claims description 91
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 67
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 67
- 230000014509 gene expression Effects 0.000 claims description 63
- 230000001900 immune effect Effects 0.000 claims description 50
- 230000030279 gene silencing Effects 0.000 claims description 43
- 241000713666 Lentivirus Species 0.000 claims description 42
- 230000000694 effects Effects 0.000 claims description 41
- 239000013598 vector Substances 0.000 claims description 41
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 40
- 230000001413 cellular effect Effects 0.000 claims description 33
- 230000035755 proliferation Effects 0.000 claims description 30
- 238000000338 in vitro Methods 0.000 claims description 22
- 230000035772 mutation Effects 0.000 claims description 22
- 239000002773 nucleotide Substances 0.000 claims description 22
- 125000003729 nucleotide group Chemical group 0.000 claims description 22
- 239000013603 viral vector Substances 0.000 claims description 21
- 230000035899 viability Effects 0.000 claims description 20
- 206010006187 Breast cancer Diseases 0.000 claims description 19
- 208000026310 Breast neoplasm Diseases 0.000 claims description 19
- 206010033128 Ovarian cancer Diseases 0.000 claims description 19
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 19
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 19
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 19
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 15
- 230000027455 binding Effects 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 230000003308 immunostimulating effect Effects 0.000 claims description 11
- 102000053642 Catalytic RNA Human genes 0.000 claims description 10
- 108090000994 Catalytic RNA Proteins 0.000 claims description 10
- 230000001965 increasing effect Effects 0.000 claims description 10
- 108091092562 ribozyme Proteins 0.000 claims description 10
- 108091033409 CRISPR Proteins 0.000 claims description 8
- 230000000692 anti-sense effect Effects 0.000 claims description 8
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 6
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 6
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 6
- -1 OX-40 Proteins 0.000 claims description 5
- 108700027336 Suppressor of Cytokine Signaling 1 Proteins 0.000 claims description 5
- 108700019146 Transgenes Proteins 0.000 claims description 5
- 230000001717 pathogenic effect Effects 0.000 claims description 5
- 102100023530 Interleukin-1 receptor-associated kinase 3 Human genes 0.000 claims description 4
- 101710199012 Interleukin-1 receptor-associated kinase 3 Proteins 0.000 claims description 4
- 102100024779 Suppressor of cytokine signaling 1 Human genes 0.000 claims description 4
- 210000000581 natural killer T-cell Anatomy 0.000 claims description 4
- 210000000822 natural killer cell Anatomy 0.000 claims description 4
- 102100027207 CD27 antigen Human genes 0.000 claims description 3
- 108010029697 CD40 Ligand Proteins 0.000 claims description 3
- 102100032937 CD40 ligand Human genes 0.000 claims description 3
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 3
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 3
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 3
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 3
- 210000002751 lymph Anatomy 0.000 claims description 3
- 241000701161 unidentified adenovirus Species 0.000 claims description 3
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 2
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 2
- 241001430294 unidentified retrovirus Species 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 2
- 102100026882 Alpha-synuclein Human genes 0.000 claims 1
- 238000010354 CRISPR gene editing Methods 0.000 claims 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims 1
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 claims 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 claims 1
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims 1
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 claims 1
- 102000017578 LAG3 Human genes 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108060006698 EGF receptor Proteins 0.000 description 118
- 102000001301 EGF receptor Human genes 0.000 description 118
- 210000004881 tumor cell Anatomy 0.000 description 61
- 108090000623 proteins and genes Proteins 0.000 description 43
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 26
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 26
- 108020004459 Small interfering RNA Proteins 0.000 description 22
- 201000010099 disease Diseases 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 241000282414 Homo sapiens Species 0.000 description 19
- 108020004999 messenger RNA Proteins 0.000 description 19
- 238000011282 treatment Methods 0.000 description 16
- 108090000695 Cytokines Proteins 0.000 description 15
- 102000004127 Cytokines Human genes 0.000 description 15
- 230000001506 immunosuppresive effect Effects 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 230000001404 mediated effect Effects 0.000 description 14
- 230000028327 secretion Effects 0.000 description 14
- 230000008685 targeting Effects 0.000 description 13
- 239000013612 plasmid Substances 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 12
- 239000011651 chromium Substances 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 206010062016 Immunosuppression Diseases 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 230000004663 cell proliferation Effects 0.000 description 10
- 230000004083 survival effect Effects 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 8
- 230000009089 cytolysis Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000004806 packaging method and process Methods 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 230000002062 proliferating effect Effects 0.000 description 7
- 238000010361 transduction Methods 0.000 description 7
- 230000026683 transduction Effects 0.000 description 7
- 230000005909 tumor killing Effects 0.000 description 7
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 6
- 206010010144 Completed suicide Diseases 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 6
- 229910052804 chromium Inorganic materials 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 108091008582 intracellular receptors Proteins 0.000 description 6
- 102000027411 intracellular receptors Human genes 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 206010067484 Adverse reaction Diseases 0.000 description 5
- 108020005544 Antisense RNA Proteins 0.000 description 5
- 108010074708 B7-H1 Antigen Proteins 0.000 description 5
- 102000008096 B7-H1 Antigen Human genes 0.000 description 5
- 208000003174 Brain Neoplasms Diseases 0.000 description 5
- 206010057248 Cell death Diseases 0.000 description 5
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 5
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 5
- 230000006838 adverse reaction Effects 0.000 description 5
- 230000003321 amplification Effects 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 239000003184 complementary RNA Substances 0.000 description 5
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 125000006850 spacer group Chemical group 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 108010083359 Antigen Receptors Proteins 0.000 description 4
- 102000006306 Antigen Receptors Human genes 0.000 description 4
- 108020004491 Antisense DNA Proteins 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 4
- 206010018338 Glioma Diseases 0.000 description 4
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 4
- 101710092458 Lymphocyte activation gene 3 protein Proteins 0.000 description 4
- 108010052285 Membrane Proteins Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 230000024932 T cell mediated immunity Effects 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000002424 anti-apoptotic effect Effects 0.000 description 4
- 239000003816 antisense DNA Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000004186 co-expression Effects 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000009368 gene silencing by RNA Effects 0.000 description 4
- 108020001756 ligand binding domains Proteins 0.000 description 4
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000009696 proliferative response Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 230000004568 DNA-binding Effects 0.000 description 3
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 3
- 108091028113 Trans-activating crRNA Proteins 0.000 description 3
- 101710185494 Zinc finger protein Proteins 0.000 description 3
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 108091032955 Bacterial small RNA Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102100035273 E3 ubiquitin-protein ligase CBL-B Human genes 0.000 description 2
- 101710141336 E3 ubiquitin-protein ligase CBL-B Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 101000977768 Homo sapiens Interleukin-1 receptor-associated kinase 3 Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 239000012979 RPMI medium Substances 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000005782 double-strand break Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 230000002518 glial effect Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 102000046801 human IRAK3 Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 108010056030 retronectin Proteins 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 230000011664 signaling Effects 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
- 229960004964 temozolomide Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 101150039808 Egfr gene Proteins 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 101000687790 Homo sapiens Suppressor of cytokine signaling 1 Proteins 0.000 description 1
- 101000830570 Homo sapiens Tumor necrosis factor alpha-induced protein 3 Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 101150102264 IE gene Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 101100219625 Mus musculus Casd1 gene Proteins 0.000 description 1
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
- 108010077854 Natural Killer Cell Receptors Proteins 0.000 description 1
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108091081548 Palindromic sequence Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm 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
- 102100037935 Polyubiquitin-C Human genes 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
- 101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 1
- 108020005093 RNA Precursors Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 241001068295 Replication defective viruses Species 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102000003661 Ribonuclease III Human genes 0.000 description 1
- 108010057163 Ribonuclease III Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 241000713311 Simian immunodeficiency virus Species 0.000 description 1
- 101150045565 Socs1 gene Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000058018 Suppressor of Cytokine Signaling 1 Human genes 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 229940126530 T cell activator Drugs 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 108010056354 Ubiquitin C Proteins 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000011942 biocatalyst Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 101150055766 cat gene Proteins 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000029578 entry into host Effects 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 108700021358 erbB-1 Genes Proteins 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 108700004026 gag Genes Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000029824 high grade glioma Diseases 0.000 description 1
- 102000058192 human SOCS1 Human genes 0.000 description 1
- 102000045235 human TNFAIP3 Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 229940126546 immune checkpoint molecule Drugs 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 201000011614 malignant glioma Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 201000003733 ovarian melanoma Diseases 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000006807 siRNA silencing Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
-
- 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
- A61K39/464403—Receptors for growth factors
- A61K39/464404—Epidermal growth factor receptors [EGFR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15021—Viruses as such, e.g. new isolates, mutants or their genomic sequences
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Abstract
L'invention concerne un lymphocyte transgénique, une construction et une composition thérapeutique ainsi qu'un procédé pour traiter un cancer. Le lymphocyte transgénique voit son point de contrôle cellulaire inactivé, il exprime un EGFR non fonctionnel et il exprime un récepteur d'antigène chimérique, le récepteur d'antigène chimérique comprenant : une région extracellulaire, la région extracellulaire comprenant une région variable de chaîne lourde et une région variable de chaîne légère d'un anticorps monocaténaire, et l'anticorps monocaténaire identifiant précisément l'antigène EGFRvIII; une région transmembranaire, la région transmembranaire étant reliée à la région extracellulaire et étant incorporée dans la membrane cellulaire des lymphocytes T; et une région intracellulaire, la région intracellulaire étant reliée à la région transmembranaire et la région intracellulaire comprenant un segment intracellulaire de CD28 ou 4-1BB et une chaîne CD3ζ.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610021438.7 | 2016-01-13 | ||
| CN201610021438.7A CN106967681B (zh) | 2016-01-13 | 2016-01-13 | 治疗脑胶质母细胞瘤的治疗组合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2017120998A1 true WO2017120998A1 (fr) | 2017-07-20 |
Family
ID=59310510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2016/073482 WO2017120998A1 (fr) | 2016-01-13 | 2016-02-04 | Composition thérapeutique pour traiter un glioblastome |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN106967681B (fr) |
| WO (1) | WO2017120998A1 (fr) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019074892A1 (fr) * | 2017-10-09 | 2019-04-18 | Wisconsin Alumni Research Foundation | Anticorps ciblant des cellules de type souche de glioblastome et leurs procédés d'utilisation |
| US11261428B2 (en) | 2018-03-15 | 2022-03-01 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11332713B2 (en) | 2016-11-16 | 2022-05-17 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11345932B2 (en) | 2018-05-16 | 2022-05-31 | Synthego Corporation | Methods and systems for guide RNA design and use |
| US11421228B2 (en) | 2018-03-15 | 2022-08-23 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109750066A (zh) * | 2017-11-01 | 2019-05-14 | 艾生命序公司 | 分泌型抗免疫检查点抗体、胞内免疫检查点抑制分子及tEGFR分子的共表达及其应用 |
| CN109750067A (zh) * | 2017-11-01 | 2019-05-14 | 艾生命序公司 | 分泌型抗免疫检查点抗体及tEGFR分子共表达的细胞及其应用 |
| ES2908324T3 (es) | 2018-01-12 | 2022-04-28 | Curocell Inc | Células inmunes mejoradas utilizando ARNsh doble y composición que las incluye |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103596981A (zh) * | 2011-04-08 | 2014-02-19 | 美国卫生和人力服务部 | 抗-表皮生长因子受体变体iii嵌合抗原受体及其用于治疗癌症的用途 |
| WO2014130657A1 (fr) * | 2013-02-20 | 2014-08-28 | The Trustees Of The University Of Pennsylvania | Traitement du cancer au moyen d'un récepteur d'antigènes chimériques anti-egfrviii humanisés |
| WO2014191128A1 (fr) * | 2013-05-29 | 2014-12-04 | Cellectis | Procédé de manipulation de cellules t pour l'immunothérapie au moyen d'un système de nucléase cas guidé par l'arn |
| WO2014201021A2 (fr) * | 2013-06-10 | 2014-12-18 | Dana-Farber Cancer Institute, Inc. | Procédés et compositions pour réduire l'immunodépression par des cellules tumorales |
-
2016
- 2016-01-13 CN CN201610021438.7A patent/CN106967681B/zh active Active
- 2016-02-04 WO PCT/CN2016/073482 patent/WO2017120998A1/fr active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103596981A (zh) * | 2011-04-08 | 2014-02-19 | 美国卫生和人力服务部 | 抗-表皮生长因子受体变体iii嵌合抗原受体及其用于治疗癌症的用途 |
| WO2014130657A1 (fr) * | 2013-02-20 | 2014-08-28 | The Trustees Of The University Of Pennsylvania | Traitement du cancer au moyen d'un récepteur d'antigènes chimériques anti-egfrviii humanisés |
| WO2014191128A1 (fr) * | 2013-05-29 | 2014-12-04 | Cellectis | Procédé de manipulation de cellules t pour l'immunothérapie au moyen d'un système de nucléase cas guidé par l'arn |
| WO2014201021A2 (fr) * | 2013-06-10 | 2014-12-18 | Dana-Farber Cancer Institute, Inc. | Procédés et compositions pour réduire l'immunodépression par des cellules tumorales |
Non-Patent Citations (4)
| Title |
|---|
| K IWAMURA: "siRNA-mediated silencing of PD-1 ligands enhances tumor- specific human T- cell effector functions", GENE THERAPY, vol. 19, no. 10, 31 October 2012 (2012-10-31), pages 959 - 966, XP055531140, ISSN: 0969-7128, DOI: doi:10.1038/gt.2011.185 * |
| LYNSEY M WHILDING ET AL.: "ErbB-targeted CAR T- cell immunotherapy of cancer", IMMUNOTHERAPY, vol. 7, no. 3, 25 March 2015 (2015-03-25) - 31 March 2015 (2015-03-31), pages 229 - 241, ISSN: 1750-743X, DOI: 10.2217/imt.14.120 * |
| MICHAEL C. JENSEN: "Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells", IMMUNOLOGICAL REVIEWS, vol. 257, no. 1, 31 January 2014 (2014-01-31), pages 127 - 144, XP055533644, ISSN: 0105-2896, DOI: doi:10.1111/imr.12139 * |
| XIULI WANG: "A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells", BLOOD, vol. 118, no. 5, 4 August 2011 (2011-08-04), pages 1255 - 1263, XP055062819, ISSN: 1528-0020, DOI: doi:10.1182/blood-2011-02-337360 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11332713B2 (en) | 2016-11-16 | 2022-05-17 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| WO2019074892A1 (fr) * | 2017-10-09 | 2019-04-18 | Wisconsin Alumni Research Foundation | Anticorps ciblant des cellules de type souche de glioblastome et leurs procédés d'utilisation |
| US11780932B2 (en) | 2017-10-09 | 2023-10-10 | Wisconsin Alumni Research Foundation | Antibodies targeting glioblastoma stem-like cells and methods of use thereof |
| US11261428B2 (en) | 2018-03-15 | 2022-03-01 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11421228B2 (en) | 2018-03-15 | 2022-08-23 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11459544B2 (en) | 2018-03-15 | 2022-10-04 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11608500B2 (en) | 2018-03-15 | 2023-03-21 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11345932B2 (en) | 2018-05-16 | 2022-05-31 | Synthego Corporation | Methods and systems for guide RNA design and use |
| US11697827B2 (en) | 2018-05-16 | 2023-07-11 | Synthego Corporation | Systems and methods for gene modification |
| US11802296B2 (en) | 2018-05-16 | 2023-10-31 | Synthego Corporation | Methods and systems for guide RNA design and use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106967681B (zh) | 2020-06-05 |
| CN106967681A (zh) | 2017-07-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2017120996A1 (fr) | Lymphocyte transgénique co-exprimant le récepteur d'antigène chimérique egfrviii et la molécule inhibitrice du point de contrôle immunitaire cellulaire et utilisation du lymphocyte | |
| WO2017120998A1 (fr) | Composition thérapeutique pour traiter un glioblastome | |
| JP6930762B2 (ja) | ヒトＰＤ−１をノックダウンしたｓｉＲＮＡ、組換え発現ＣＡＲ−Ｔベクターおよびその構築方法と使用 | |
| CN108018299B (zh) | 靶向bcma的嵌合抗原受体及其用途 | |
| JP6538716B2 (ja) | Ｍｎｄプロモーターのキメラ抗原受容体 | |
| US20210196756A1 (en) | Anti-cd19 car-t cell | |
| WO2018137295A1 (fr) | Lymphocyte transgénique co-exprimant le récepteur antigénique chimérique anti-msln et molécule inhibitrice de point de contrôle immunitaire et leur utilisation | |
| WO2018006880A1 (fr) | Co-expression d'un récepteur de point de contrôle immunitaire recombinant et d'un inhibiteur du point de contrôle immunitaire et application | |
| WO2018137293A1 (fr) | Composition thérapeutique pour le traitement d'une tumeur à mésothéline positive | |
| WO2017133174A1 (fr) | Composition thérapeutique pour le traitement de la leucémie à cellules b et du lymphome à cellules b | |
| US20210213119A1 (en) | Improved therapeutic t cell | |
| WO2022007804A1 (fr) | Lymphocyte t et son utilisation | |
| WO2020083282A1 (fr) | Anticorps pd-l1 sécrétant des lymphocytes car-t anti-mésothéline pour l'immunothérapie antitumorale | |
| WO2018006881A1 (fr) | Récepteur de point de contrôle immunitaire recombinant et son application | |
| CN111212903A (zh) | 具有自杀基因开关的靶向人间皮素的工程化免疫细胞 | |
| WO2017028374A1 (fr) | Construction, lymphocyte génétiquement modifié, son procédé de préparation et utilisation associée | |
| JP7233720B2 (ja) | ヒトメソセリンを特異的に認識する細胞表面分子、ｉｌ－７、及びｃｃｌ１９を発現する免疫担当細胞 | |
| CN114517185B (zh) | 嵌合抗原受体nk细胞及其制备方法和应用 | |
| WO2018137294A1 (fr) | Récepteur antigénique chimérique anti-msln co-exprimant un lymphocyte transgénique, et egfr non fonctionnel et son utilisation | |
| WO2017120997A1 (fr) | Lymphocyte transgénique co-exprimant le récepteur d'antigène chimère egfrviii et un egfr non fonctionnel et utilisations du lymphocyte | |
| CN112852741A (zh) | 一种嵌合抗原受体t细胞及其制备方法和细胞药物 | |
| CN113646426A (zh) | 一种包含肿瘤抗原识别受体的免疫细胞及其应用 | |
| CN114058589B (zh) | 具有嵌合抗原受体修饰的免疫细胞、制备方法和药物 | |
| CN113549157B (zh) | 双靶向嵌合抗原受体及其应用 | |
| KR102521500B1 (ko) | 증진된 효능을 갖는 면역세포 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 16884560 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 16884560 Country of ref document: EP Kind code of ref document: A1 |