CA2973524A1 - Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy - Google Patents
Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy Download PDFInfo
- Publication number
- CA2973524A1 CA2973524A1 CA2973524A CA2973524A CA2973524A1 CA 2973524 A1 CA2973524 A1 CA 2973524A1 CA 2973524 A CA2973524 A CA 2973524A CA 2973524 A CA2973524 A CA 2973524A CA 2973524 A1 CA2973524 A1 CA 2973524A1
- Authority
- CA
- Canada
- Prior art keywords
- hsp70
- epitope1
- cell
- seq
- chimeric antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 title claims abstract description 429
- 238000002619 cancer immunotherapy Methods 0.000 title description 3
- 210000004027 cell Anatomy 0.000 claims abstract description 474
- 210000002865 immune cell Anatomy 0.000 claims abstract description 155
- 239000000427 antigen Substances 0.000 claims abstract description 73
- 108091007433 antigens Proteins 0.000 claims abstract description 73
- 102000036639 antigens Human genes 0.000 claims abstract description 73
- 230000027455 binding Effects 0.000 claims abstract description 71
- 208000032839 leukemia Diseases 0.000 claims abstract description 30
- 239000012528 membrane Substances 0.000 claims abstract description 24
- 101710163595 Chaperone protein DnaK Proteins 0.000 claims description 225
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 claims description 225
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 claims description 224
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 172
- 238000000034 method Methods 0.000 claims description 122
- 108020001756 ligand binding domains Proteins 0.000 claims description 95
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 91
- 239000003814 drug Substances 0.000 claims description 88
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 87
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 claims description 85
- 206010028980 Neoplasm Diseases 0.000 claims description 85
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 82
- 230000011664 signaling Effects 0.000 claims description 82
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 76
- 229940079593 drug Drugs 0.000 claims description 73
- 229920001184 polypeptide Polymers 0.000 claims description 72
- 230000001413 cellular effect Effects 0.000 claims description 65
- 201000011510 cancer Diseases 0.000 claims description 62
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 56
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 56
- 241000282414 Homo sapiens Species 0.000 claims description 47
- 102000040430 polynucleotide Human genes 0.000 claims description 46
- 108091033319 polynucleotide Proteins 0.000 claims description 46
- 239000002157 polynucleotide Substances 0.000 claims description 46
- 230000014509 gene expression Effects 0.000 claims description 45
- 210000004896 polypeptide structure Anatomy 0.000 claims description 44
- 230000001086 cytosolic effect Effects 0.000 claims description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 150000007523 nucleic acids Chemical class 0.000 claims description 43
- 238000002560 therapeutic procedure Methods 0.000 claims description 41
- 201000010099 disease Diseases 0.000 claims description 33
- 102000039446 nucleic acids Human genes 0.000 claims description 31
- 108020004707 nucleic acids Proteins 0.000 claims description 31
- 150000001413 amino acids Chemical group 0.000 claims description 30
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 28
- 201000005787 hematologic cancer Diseases 0.000 claims description 16
- 230000003211 malignant effect Effects 0.000 claims description 16
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 14
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 14
- 239000004471 Glycine Substances 0.000 claims description 12
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 10
- 229960004641 rituximab Drugs 0.000 claims description 10
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 9
- 230000002489 hematologic effect Effects 0.000 claims description 9
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 9
- 229960000548 alemtuzumab Drugs 0.000 claims description 7
- 230000001105 regulatory effect Effects 0.000 claims description 7
- 102220080600 rs797046116 Human genes 0.000 claims description 6
- 229960005395 cetuximab Drugs 0.000 claims description 5
- 239000013604 expression vector Substances 0.000 claims description 5
- 230000006028 immune-suppresssive effect Effects 0.000 claims description 5
- 229960000402 palivizumab Drugs 0.000 claims description 5
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 claims description 4
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 claims description 4
- 229940044683 chemotherapy drug Drugs 0.000 claims description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 4
- 230000000779 depleting effect Effects 0.000 claims description 4
- 108010066358 heat-shock protein 70.1 Proteins 0.000 claims description 4
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 claims description 3
- MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 claims description 3
- 101710181340 Chaperone protein DnaK2 Proteins 0.000 claims description 3
- 102100040407 Heat shock 70 kDa protein 1B Human genes 0.000 claims description 3
- 229960000446 abciximab Drugs 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 229960002964 adalimumab Drugs 0.000 claims description 3
- 229960004669 basiliximab Drugs 0.000 claims description 3
- 229960003270 belimumab Drugs 0.000 claims description 3
- 229960000397 bevacizumab Drugs 0.000 claims description 3
- 229960000455 brentuximab vedotin Drugs 0.000 claims description 3
- 229960001838 canakinumab Drugs 0.000 claims description 3
- 229960003115 certolizumab pegol Drugs 0.000 claims description 3
- 230000000295 complement effect Effects 0.000 claims description 3
- 229960002806 daclizumab Drugs 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- 229960001251 denosumab Drugs 0.000 claims description 3
- 229960002224 eculizumab Drugs 0.000 claims description 3
- 229960000284 efalizumab Drugs 0.000 claims description 3
- 229960000578 gemtuzumab Drugs 0.000 claims description 3
- 229960001743 golimumab Drugs 0.000 claims description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 229960000598 infliximab Drugs 0.000 claims description 3
- 229960005386 ipilimumab Drugs 0.000 claims description 3
- 229960003816 muromonab-cd3 Drugs 0.000 claims description 3
- 229960005027 natalizumab Drugs 0.000 claims description 3
- 229960002450 ofatumumab Drugs 0.000 claims description 3
- 229960000470 omalizumab Drugs 0.000 claims description 3
- 229960001972 panitumumab Drugs 0.000 claims description 3
- 229960003876 ranibizumab Drugs 0.000 claims description 3
- 229960003989 tocilizumab Drugs 0.000 claims description 3
- 229960005267 tositumomab Drugs 0.000 claims description 3
- 229960000575 trastuzumab Drugs 0.000 claims description 3
- 229960003824 ustekinumab Drugs 0.000 claims description 3
- 229960004914 vedolizumab Drugs 0.000 claims description 3
- 239000003446 ligand Substances 0.000 abstract description 19
- 230000009257 reactivity Effects 0.000 abstract description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 abstract description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 abstract description 3
- 230000036039 immunity Effects 0.000 abstract description 3
- 108090000623 proteins and genes Proteins 0.000 description 182
- 238000011282 treatment Methods 0.000 description 62
- 239000013598 vector Substances 0.000 description 59
- 108091008874 T cell receptors Proteins 0.000 description 56
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 55
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 53
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 52
- 206010059866 Drug resistance Diseases 0.000 description 48
- 125000003275 alpha amino acid group Chemical group 0.000 description 46
- 108010042407 Endonucleases Proteins 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 33
- 235000018102 proteins Nutrition 0.000 description 32
- 102000053602 DNA Human genes 0.000 description 30
- 108020004414 DNA Proteins 0.000 description 30
- 235000001014 amino acid Nutrition 0.000 description 30
- 239000000203 mixture Substances 0.000 description 28
- 108020004999 messenger RNA Proteins 0.000 description 27
- 230000000415 inactivating effect Effects 0.000 description 26
- 102100031780 Endonuclease Human genes 0.000 description 25
- 241000699666 Mus <mouse, genus> Species 0.000 description 25
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 23
- 238000005520 cutting process Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- 230000001225 therapeutic effect Effects 0.000 description 22
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 21
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 21
- 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 20
- 239000002246 antineoplastic agent Substances 0.000 description 20
- -1 OX-40 (CD134) Proteins 0.000 description 18
- 230000000735 allogeneic effect Effects 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 238000002347 injection Methods 0.000 description 18
- 239000007924 injection Substances 0.000 description 18
- 230000035755 proliferation Effects 0.000 description 18
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 17
- 230000004913 activation Effects 0.000 description 17
- 238000009169 immunotherapy Methods 0.000 description 17
- 238000001890 transfection Methods 0.000 description 17
- 238000005516 engineering process Methods 0.000 description 16
- 230000000670 limiting effect Effects 0.000 description 16
- 102000004631 Calcineurin Human genes 0.000 description 15
- 108010042955 Calcineurin Proteins 0.000 description 15
- 241000283973 Oryctolagus cuniculus Species 0.000 description 15
- 108010022394 Threonine synthase Proteins 0.000 description 15
- 102000004419 dihydrofolate reductase Human genes 0.000 description 15
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 14
- 125000003729 nucleotide group Chemical group 0.000 description 14
- 230000001235 sensitizing effect Effects 0.000 description 14
- 102100040352 Heat shock 70 kDa protein 1A Human genes 0.000 description 13
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 13
- 230000003197 catalytic effect Effects 0.000 description 13
- 230000002779 inactivation Effects 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 230000035772 mutation Effects 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 108020004705 Codon Proteins 0.000 description 12
- 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 12
- 125000000539 amino acid group Chemical group 0.000 description 12
- 238000002512 chemotherapy Methods 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 229960000485 methotrexate Drugs 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 229960003087 tioguanine Drugs 0.000 description 12
- 108091033409 CRISPR Proteins 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 11
- 229940041181 antineoplastic drug Drugs 0.000 description 11
- 210000000349 chromosome Anatomy 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 10
- 102000004533 Endonucleases Human genes 0.000 description 10
- 101001076642 Homo sapiens Inosine-5'-monophosphate dehydrogenase 2 Proteins 0.000 description 10
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 10
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 210000001185 bone marrow Anatomy 0.000 description 10
- 238000003501 co-culture Methods 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000004927 fusion Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229930002330 retinoic acid Natural products 0.000 description 10
- 210000000130 stem cell Anatomy 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 230000005945 translocation Effects 0.000 description 10
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 9
- 102100029588 Deoxycytidine kinase Human genes 0.000 description 9
- 108010033174 Deoxycytidine kinase Proteins 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 9
- 101710163270 Nuclease Proteins 0.000 description 9
- 102100029452 T cell receptor alpha chain constant Human genes 0.000 description 9
- 229910052785 arsenic Inorganic materials 0.000 description 9
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 229960000975 daunorubicin Drugs 0.000 description 9
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 229920002477 rna polymer Polymers 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 229960001727 tretinoin Drugs 0.000 description 9
- 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 8
- 108010036949 Cyclosporine Proteins 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 8
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 8
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 8
- 102100025891 Inosine-5'-monophosphate dehydrogenase 2 Human genes 0.000 description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 239000004472 Lysine Substances 0.000 description 8
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 8
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 229940127089 cytotoxic agent Drugs 0.000 description 8
- 238000004520 electroporation Methods 0.000 description 8
- 238000002744 homologous recombination Methods 0.000 description 8
- 230000006801 homologous recombination Effects 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 229960001156 mitoxantrone Drugs 0.000 description 8
- 230000008685 targeting Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000013603 viral vector Substances 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 229930105110 Cyclosporin A Natural products 0.000 description 7
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 7
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 102000000588 Interleukin-2 Human genes 0.000 description 7
- 239000000232 Lipid Bilayer Substances 0.000 description 7
- 206010048723 Multiple-drug resistance Diseases 0.000 description 7
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 7
- 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 7
- 238000007792 addition Methods 0.000 description 7
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 7
- 229960001220 amsacrine Drugs 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 7
- 229960000928 clofarabine Drugs 0.000 description 7
- 229960000684 cytarabine Drugs 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 7
- 238000012239 gene modification Methods 0.000 description 7
- 210000004408 hybridoma Anatomy 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 210000003705 ribosome Anatomy 0.000 description 7
- 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 7
- 238000012360 testing method Methods 0.000 description 7
- 230000002463 transducing effect Effects 0.000 description 7
- 238000011426 transformation method Methods 0.000 description 7
- 230000035899 viability Effects 0.000 description 7
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 6
- 101100508818 Mus musculus Inpp5k gene Proteins 0.000 description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 description 6
- 101100366438 Rattus norvegicus Sphkap gene Proteins 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 230000005017 genetic modification Effects 0.000 description 6
- 235000013617 genetically modified food Nutrition 0.000 description 6
- 230000016784 immunoglobulin production Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 201000000050 myeloid neoplasm Diseases 0.000 description 6
- 230000006780 non-homologous end joining Effects 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 230000019491 signal transduction Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 238000010361 transduction Methods 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 5
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 5
- 108060002716 Exonuclease Proteins 0.000 description 5
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 5
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 5
- 101001037759 Homo sapiens Heat shock 70 kDa protein 1A Proteins 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 5
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 5
- 102100025825 Methylated-DNA-protein-cysteine methyltransferase Human genes 0.000 description 5
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 229940045799 anthracyclines and related substance Drugs 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 229960004630 chlorambucil Drugs 0.000 description 5
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 5
- 229960001265 ciclosporin Drugs 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 102000013165 exonuclease Human genes 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 229960000390 fludarabine Drugs 0.000 description 5
- 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 5
- 239000004052 folic acid antagonist Substances 0.000 description 5
- 239000000833 heterodimer Substances 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 5
- 229960004961 mechlorethamine Drugs 0.000 description 5
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 5
- 108040008770 methylated-DNA-[protein]-cysteine S-methyltransferase activity proteins Proteins 0.000 description 5
- 230000037361 pathway 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
- 239000000523 sample Substances 0.000 description 5
- 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 5
- 235000000346 sugar Nutrition 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 4
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- 101000964894 Bos taurus 14-3-3 protein zeta/delta Proteins 0.000 description 4
- 102100024263 CD160 antigen Human genes 0.000 description 4
- 102100026548 Caspase-8 Human genes 0.000 description 4
- 101710181333 Chaperone protein dnaK1 Proteins 0.000 description 4
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 4
- 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 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 4
- 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 description 4
- 102100038006 High affinity immunoglobulin epsilon receptor subunit alpha Human genes 0.000 description 4
- 108050001540 High affinity immunoglobulin epsilon receptor subunit beta Proteins 0.000 description 4
- 101000824278 Homo sapiens Acyl-[acyl-carrier-protein] hydrolase Proteins 0.000 description 4
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 4
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 4
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 4
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 4
- 101000884270 Homo sapiens Natural killer cell receptor 2B4 Proteins 0.000 description 4
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 4
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 102000017578 LAG3 Human genes 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 4
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 4
- 206010027457 Metastases to liver Diseases 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 description 4
- KRWMERLEINMZFT-UHFFFAOYSA-N O6-benzylguanine Chemical compound C=12NC=NC2=NC(N)=NC=1OCC1=CC=CC=C1 KRWMERLEINMZFT-UHFFFAOYSA-N 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 4
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 230000006044 T cell activation Effects 0.000 description 4
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 4
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 101150038738 ble gene Proteins 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 239000012829 chemotherapy agent Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002784 cytotoxicity assay Methods 0.000 description 4
- 231100000263 cytotoxicity test Toxicity 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000005782 double-strand break Effects 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 4
- 238000001476 gene delivery Methods 0.000 description 4
- 238000001415 gene therapy Methods 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 101150023497 mcrA gene Proteins 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 239000013600 plasmid vector Substances 0.000 description 4
- 210000004986 primary T-cell Anatomy 0.000 description 4
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 4
- 229960000624 procarbazine Drugs 0.000 description 4
- 108020001580 protein domains Proteins 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003212 purines Chemical class 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 229960004964 temozolomide Drugs 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 229960004799 tryptophan Drugs 0.000 description 4
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- CDKIEBFIMCSCBB-UHFFFAOYSA-N 1-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-3-(1-methyl-2-phenylpyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one;hydrochloride Chemical compound Cl.C1C=2C=C(OC)C(OC)=CC=2CCN1C(=O)C=CC(C1=CC=CN=C1N1C)=C1C1=CC=CC=C1 CDKIEBFIMCSCBB-UHFFFAOYSA-N 0.000 description 3
- 102100038078 CD276 antigen Human genes 0.000 description 3
- 101150013553 CD40 gene Proteins 0.000 description 3
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 3
- 102100035793 CD83 antigen Human genes 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 102100026549 Caspase-10 Human genes 0.000 description 3
- 102100029855 Caspase-3 Human genes 0.000 description 3
- 102100038918 Caspase-6 Human genes 0.000 description 3
- 102100038902 Caspase-7 Human genes 0.000 description 3
- 206010050685 Cytokine storm Diseases 0.000 description 3
- 102000000311 Cytosine Deaminase Human genes 0.000 description 3
- 108010080611 Cytosine Deaminase Proteins 0.000 description 3
- 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 0.000 description 3
- 230000007018 DNA scission Effects 0.000 description 3
- 102100026693 FAS-associated death domain protein Human genes 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 3
- 102100040754 Guanylate cyclase soluble subunit alpha-1 Human genes 0.000 description 3
- 102100040735 Guanylate cyclase soluble subunit alpha-2 Human genes 0.000 description 3
- 102100040739 Guanylate cyclase soluble subunit beta-1 Human genes 0.000 description 3
- 102100028963 Guanylate cyclase soluble subunit beta-2 Human genes 0.000 description 3
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 3
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 3
- 102100028008 Heme oxygenase 2 Human genes 0.000 description 3
- 102100035081 Homeobox protein TGIF1 Human genes 0.000 description 3
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 3
- 101000983518 Homo sapiens Caspase-10 Proteins 0.000 description 3
- 101000741087 Homo sapiens Caspase-6 Proteins 0.000 description 3
- 101000741014 Homo sapiens Caspase-7 Proteins 0.000 description 3
- 101000983528 Homo sapiens Caspase-8 Proteins 0.000 description 3
- 101000911074 Homo sapiens FAS-associated death domain protein Proteins 0.000 description 3
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 3
- 101001038755 Homo sapiens Guanylate cyclase soluble subunit alpha-1 Proteins 0.000 description 3
- 101001038749 Homo sapiens Guanylate cyclase soluble subunit alpha-2 Proteins 0.000 description 3
- 101001038731 Homo sapiens Guanylate cyclase soluble subunit beta-1 Proteins 0.000 description 3
- 101001059095 Homo sapiens Guanylate cyclase soluble subunit beta-2 Proteins 0.000 description 3
- 101001079615 Homo sapiens Heme oxygenase 2 Proteins 0.000 description 3
- 101000596925 Homo sapiens Homeobox protein TGIF1 Proteins 0.000 description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 3
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 3
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 3
- 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 description 3
- 101001091194 Homo sapiens Peptidyl-prolyl cis-trans isomerase G Proteins 0.000 description 3
- 101000692259 Homo sapiens Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 Proteins 0.000 description 3
- 101001068027 Homo sapiens Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Proteins 0.000 description 3
- 101001068019 Homo sapiens Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform Proteins 0.000 description 3
- 101000688930 Homo sapiens Signaling threshold-regulating transmembrane adapter 1 Proteins 0.000 description 3
- 101000688996 Homo sapiens Ski-like protein Proteins 0.000 description 3
- 101000740162 Homo sapiens Sodium- and chloride-dependent transporter XTRP3 Proteins 0.000 description 3
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 3
- 101000830950 Homo sapiens Three prime repair exonuclease 2 Proteins 0.000 description 3
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 3
- 101000922131 Homo sapiens Tyrosine-protein kinase CSK Proteins 0.000 description 3
- 101001135589 Homo sapiens Tyrosine-protein phosphatase non-receptor type 22 Proteins 0.000 description 3
- 101000617285 Homo sapiens Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 description 3
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 3
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 3
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 3
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 3
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 3
- 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- 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 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 108060004795 Methyltransferase Proteins 0.000 description 3
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 3
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 3
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 3
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 3
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 3
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 3
- 102000011279 Multidrug resistance protein 1 Human genes 0.000 description 3
- 101100395818 Mus musculus Hspa2 gene Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 102100024894 PR domain zinc finger protein 1 Human genes 0.000 description 3
- 102100026066 Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 Human genes 0.000 description 3
- 241000709664 Picornaviridae Species 0.000 description 3
- 108010009975 Positive Regulatory Domain I-Binding Factor 1 Proteins 0.000 description 3
- 101100339696 Rattus norvegicus Hspa1b gene Proteins 0.000 description 3
- 102100034464 Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Human genes 0.000 description 3
- 102100034470 Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform Human genes 0.000 description 3
- 102100029946 Sialic acid-binding Ig-like lectin 7 Human genes 0.000 description 3
- 102100024453 Signaling threshold-regulating transmembrane adapter 1 Human genes 0.000 description 3
- 241000700584 Simplexvirus Species 0.000 description 3
- 102100029969 Ski oncogene Human genes 0.000 description 3
- 102100024451 Ski-like protein Human genes 0.000 description 3
- 101000987219 Sus scrofa Pregnancy-associated glycoprotein 1 Proteins 0.000 description 3
- 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 description 3
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 3
- 108091007178 TNFRSF10A Proteins 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 108091028113 Trans-activating crRNA Proteins 0.000 description 3
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 3
- 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 3
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 3
- 102100031167 Tyrosine-protein kinase CSK Human genes 0.000 description 3
- 102100033138 Tyrosine-protein phosphatase non-receptor type 22 Human genes 0.000 description 3
- 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 238000011316 allogeneic transplantation Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000003432 anti-folate effect Effects 0.000 description 3
- 230000000340 anti-metabolite Effects 0.000 description 3
- 229940127074 antifolate Drugs 0.000 description 3
- 229940100197 antimetabolite Drugs 0.000 description 3
- 239000002256 antimetabolite Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 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 3
- 238000001574 biopsy Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000002659 cell therapy Methods 0.000 description 3
- 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 description 3
- 229930182912 cyclosporin Natural products 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000002559 cytogenic effect Effects 0.000 description 3
- 206010052015 cytokine release syndrome Diseases 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000009093 first-line therapy Methods 0.000 description 3
- 238000010362 genome editing Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 201000010536 head and neck cancer Diseases 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000005965 immune activity Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 229940125721 immunosuppressive agent Drugs 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 229960001428 mercaptopurine Drugs 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 210000004214 philadelphia chromosome Anatomy 0.000 description 3
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 3
- 229960004618 prednisone Drugs 0.000 description 3
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 239000002213 purine nucleotide Substances 0.000 description 3
- 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 3
- 230000007420 reactivation Effects 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229960002930 sirolimus Drugs 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- MXBUWHDMZGKTHK-INIZCTEOSA-N (2s)-2-[[4-[[(2-amino-4-oxo-1h-quinazolin-6-yl)amino]methyl]benzoyl]amino]pentanedioic acid Chemical compound C=1C=C2NC(N)=NC(=O)C2=CC=1NCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MXBUWHDMZGKTHK-INIZCTEOSA-N 0.000 description 2
- UBQKVJZIMQFZFL-UHFFFAOYSA-N 1,1-dichloro-3-nitrosourea Chemical compound ClN(Cl)C(=O)NN=O UBQKVJZIMQFZFL-UHFFFAOYSA-N 0.000 description 2
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 2
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 2
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 102000006306 Antigen Receptors Human genes 0.000 description 2
- 108010083359 Antigen Receptors Proteins 0.000 description 2
- 241000710189 Aphthovirus Species 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 2
- 102100027207 CD27 antigen Human genes 0.000 description 2
- 108010065524 CD52 Antigen Proteins 0.000 description 2
- 238000010453 CRISPR/Cas method Methods 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102100026550 Caspase-9 Human genes 0.000 description 2
- 108090000566 Caspase-9 Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- 208000036566 Erythroleukaemia Diseases 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 2
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
- 101000927313 Homo sapiens DNA replication ATP-dependent helicase DNA2 Proteins 0.000 description 2
- 101100339687 Homo sapiens HSPA1A gene Proteins 0.000 description 2
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 2
- 101000863882 Homo sapiens Sialic acid-binding Ig-like lectin 7 Proteins 0.000 description 2
- 101000863883 Homo sapiens Sialic acid-binding Ig-like lectin 9 Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 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
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- 102000016397 Methyltransferase Human genes 0.000 description 2
- 108010006519 Molecular Chaperones Proteins 0.000 description 2
- 229930191564 Monensin Natural products 0.000 description 2
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 2
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 2
- 102100021339 Multidrug resistance-associated protein 1 Human genes 0.000 description 2
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 108010047620 Phytohemagglutinins Proteins 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 2
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- 102100029965 Sialic acid-binding Ig-like lectin 9 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108700042076 T-Cell Receptor alpha Genes Proteins 0.000 description 2
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 2
- 102100024872 Three prime repair exonuclease 2 Human genes 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000004357 Transferases Human genes 0.000 description 2
- 108090000992 Transferases Proteins 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- 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 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 238000010317 ablation therapy Methods 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 208000021841 acute erythroid leukemia Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 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 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000011394 anticancer treatment Methods 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 239000003972 antineoplastic antibiotic Substances 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 230000003190 augmentative effect Effects 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
- 229960002170 azathioprine Drugs 0.000 description 2
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 2
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 2
- OYVAGSVQBOHSSS-WXFSZRTFSA-O bleomycin Chemical compound 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](OC1C(C(O)C(O)C(CO)O1)OC1C(C(OC(N)=O)C(O)C(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 OYVAGSVQBOHSSS-WXFSZRTFSA-O 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229940112129 campath Drugs 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000012512 characterization method Methods 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
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 101150096852 dck gene Proteins 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 210000004700 fetal blood Anatomy 0.000 description 2
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 2
- 229960004413 flucytosine Drugs 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 229940014144 folate Drugs 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical class C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 102000056799 human IMPDH2 Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000005931 immune cell recruitment Effects 0.000 description 2
- 230000006450 immune cell response Effects 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 208000027866 inflammatory disease Diseases 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
- 230000004068 intracellular signaling Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 201000001268 lymphoproliferative syndrome Diseases 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 229960005358 monensin Drugs 0.000 description 2
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 229960004866 mycophenolate mofetil Drugs 0.000 description 2
- 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 2
- 210000000066 myeloid cell Anatomy 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000032965 negative regulation of cell volume Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000001885 phytohemagglutinin Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 150000003834 purine nucleoside derivatives Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000004989 spleen cell Anatomy 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
- 230000035882 stress Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 229950010127 teplizumab Drugs 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine 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-XQKSVPLYSA-N 0.000 description 2
- ZROHGHOFXNOHSO-BNTLRKBRSA-N (1r,2r)-cyclohexane-1,2-diamine;oxalic acid;platinum(2+) Chemical compound [Pt+2].OC(=O)C(O)=O.N[C@@H]1CCCC[C@H]1N ZROHGHOFXNOHSO-BNTLRKBRSA-N 0.000 description 1
- UQQHOWKTDKKTHO-ICQCTTRCSA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolane-3,4-diol Chemical compound C1=NC=2C(OC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O UQQHOWKTDKKTHO-ICQCTTRCSA-N 0.000 description 1
- YWOLSBHQLNEVOL-DNVVRKGNSA-N (2s,3s)-2-amino-3-methylpentanoic acid;(2s)-2-aminopentanedioic acid Chemical compound CC[C@H](C)[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O YWOLSBHQLNEVOL-DNVVRKGNSA-N 0.000 description 1
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- IPVFGAYTKQKGBM-BYPJNBLXSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound F[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 IPVFGAYTKQKGBM-BYPJNBLXSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-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
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 1
- 108010082808 4-1BB Ligand Proteins 0.000 description 1
- 102000002627 4-1BB Ligand Human genes 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- 102100033051 40S ribosomal protein S19 Human genes 0.000 description 1
- ZUQBAQVRAURMCL-SWLSCSKDSA-N 5,10-dideazatetrahydrofolic acid Chemical compound C([C@H]1CC=2C(=O)N=C(NC=2NC1)N)CC1=CC=C(C(=O)N[C@H](CCC(O)=O)C(O)=O)C=C1 ZUQBAQVRAURMCL-SWLSCSKDSA-N 0.000 description 1
- HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 1
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
- VJXSSYDSOJBUAV-UHFFFAOYSA-N 6-(2,5-dimethoxy-benzyl)-5-methyl-pyrido[2,3-d]pyrimidine-2,4-diamine Chemical compound COC1=CC=C(OC)C(CC=2C(=C3C(N)=NC(N)=NC3=NC=2)C)=C1 VJXSSYDSOJBUAV-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 1
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
- 208000010581 Acute myeloid leukemia with minimal differentiation Diseases 0.000 description 1
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
- 208000016585 Acute panmyelosis with myelofibrosis Diseases 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 101100279855 Arabidopsis thaliana EPFL5 gene Proteins 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 102100022970 Basic leucine zipper transcriptional factor ATF-like Human genes 0.000 description 1
- 208000033775 Basophilic Acute Leukemia Diseases 0.000 description 1
- 208000033932 Blackfan-Diamond anemia Diseases 0.000 description 1
- 208000005692 Bloom Syndrome Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100370338 Bos taurus TREX1 gene Proteins 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 102100026094 C-type lectin domain family 12 member A Human genes 0.000 description 1
- 108091016585 CD44 antigen Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 108010058590 CD47 Antigen Proteins 0.000 description 1
- 102000006355 CD47 Antigen Human genes 0.000 description 1
- 102100025221 CD70 antigen Human genes 0.000 description 1
- 101150031358 COLEC10 gene Proteins 0.000 description 1
- 108091079001 CRISPR RNA Proteins 0.000 description 1
- 101100510617 Caenorhabditis elegans sel-8 gene Proteins 0.000 description 1
- 229940122739 Calcineurin inhibitor Drugs 0.000 description 1
- 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 description 1
- 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 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 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
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108090000538 Caspase-8 Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000031404 Chromosome Aberrations Diseases 0.000 description 1
- VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 208000025212 Constitutional neutropenia Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 101710095468 Cyclase Proteins 0.000 description 1
- 241001044073 Cypa Species 0.000 description 1
- 102100026846 Cytidine deaminase Human genes 0.000 description 1
- 108010031325 Cytidine deaminase Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102100033072 DNA replication ATP-dependent helicase DNA2 Human genes 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 201000004449 Diamond-Blackfan anemia Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101710181478 Envelope glycoprotein GP350 Proteins 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101000809594 Escherichia coli (strain K12) Shikimate kinase 1 Proteins 0.000 description 1
- 241001141491 Eumorpha elisa Species 0.000 description 1
- 201000004939 Fanconi anemia Diseases 0.000 description 1
- 108090000652 Flap endonucleases Proteins 0.000 description 1
- 102000004150 Flap endonucleases Human genes 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 208000000666 Fowlpox Diseases 0.000 description 1
- 240000005702 Galium aparine Species 0.000 description 1
- 235000014820 Galium aparine Nutrition 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 241000941423 Grom virus Species 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class 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 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 1
- 108010024164 HLA-G Antigens Proteins 0.000 description 1
- 108010027814 HSP72 Heat-Shock Proteins Proteins 0.000 description 1
- 101150105682 HSPA1A gene Proteins 0.000 description 1
- 102000042775 Heat shock protein 70 family Human genes 0.000 description 1
- 108091082017 Heat shock protein 70 family Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100022132 High affinity immunoglobulin epsilon receptor subunit gamma Human genes 0.000 description 1
- 108091010847 High affinity immunoglobulin epsilon receptor subunit gamma Proteins 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000903742 Homo sapiens Basic leucine zipper transcriptional factor ATF-like Proteins 0.000 description 1
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
- 101100496086 Homo sapiens CLEC12A gene Proteins 0.000 description 1
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 1
- 101000897353 Homo sapiens Cell division cycle protein 123 homolog Proteins 0.000 description 1
- 101000980898 Homo sapiens Cell division cycle-associated protein 4 Proteins 0.000 description 1
- 101000917383 Homo sapiens Deoxycytidine kinase Proteins 0.000 description 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
- 101000988834 Homo sapiens Hypoxanthine-guanine phosphoribosyltransferase Proteins 0.000 description 1
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 1
- 101001083151 Homo sapiens Interleukin-10 receptor subunit alpha Proteins 0.000 description 1
- 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 description 1
- 101000984189 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 2 Proteins 0.000 description 1
- 101000984186 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 4 Proteins 0.000 description 1
- 101000969812 Homo sapiens Multidrug resistance-associated protein 1 Proteins 0.000 description 1
- 101000863692 Homo sapiens Ski oncogene Proteins 0.000 description 1
- 101000634853 Homo sapiens T cell receptor alpha chain constant Proteins 0.000 description 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 101000830956 Homo sapiens Three-prime repair exonuclease 1 Proteins 0.000 description 1
- 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000711920 Human orthopneumovirus Species 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010052210 Infantile genetic agranulocytosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 108010015268 Integration Host Factors Proteins 0.000 description 1
- 102100030236 Interleukin-10 receptor subunit alpha Human genes 0.000 description 1
- 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 108010052781 Interleukin-3 Receptor alpha Subunit Proteins 0.000 description 1
- 102000018883 Interleukin-3 Receptor alpha Subunit Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108020003285 Isocitrate lyase Proteins 0.000 description 1
- 208000012565 Kostmann syndrome Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 102100025583 Leukocyte immunoglobulin-like receptor subfamily B member 2 Human genes 0.000 description 1
- 102100025578 Leukocyte immunoglobulin-like receptor subfamily B member 4 Human genes 0.000 description 1
- 206010024404 Leukostasis Diseases 0.000 description 1
- 201000011062 Li-Fraumeni syndrome Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 108010091221 Lymphotoxin beta Receptor Proteins 0.000 description 1
- 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 101100178726 Mus musculus Hspa14 gene Proteins 0.000 description 1
- 101100339688 Mus musculus Hspa1a gene Proteins 0.000 description 1
- 101100339694 Mus musculus Hspa1b gene Proteins 0.000 description 1
- 101000687343 Mus musculus PR domain zinc finger protein 1 Proteins 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
- 101100370340 Mus musculus Trex1 gene Proteins 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- DYCJFJRCWPVDHY-LSCFUAHRSA-N NBMPR Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(SCC=3C=CC(=CC=3)[N+]([O-])=O)=C2N=C1 DYCJFJRCWPVDHY-LSCFUAHRSA-N 0.000 description 1
- 208000003019 Neurofibromatosis 1 Diseases 0.000 description 1
- 208000024834 Neurofibromatosis type 1 Diseases 0.000 description 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 241000714209 Norwalk virus Species 0.000 description 1
- 108091007494 Nucleic acid- binding domains Proteins 0.000 description 1
- 241000702244 Orthoreovirus Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 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
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 208000007541 Preleukemia Diseases 0.000 description 1
- 101710186352 Probable membrane antigen 3 Proteins 0.000 description 1
- 101710181078 Probable membrane antigen 75 Proteins 0.000 description 1
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 101100339690 Rattus norvegicus Hspa1a gene Proteins 0.000 description 1
- 101100451492 Rattus norvegicus Hspa1l gene Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 102000003661 Ribonuclease III Human genes 0.000 description 1
- 108010057163 Ribonuclease III Proteins 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 101710189648 Serine/threonine-protein phosphatase Proteins 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 1
- 102000001555 Sialic Acid Binding Ig-like Lectin 3 Human genes 0.000 description 1
- 108010047827 Sialic Acid Binding Immunoglobulin-like Lectins Proteins 0.000 description 1
- 102000007073 Sialic Acid Binding Immunoglobulin-like Lectins Human genes 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 231100000632 Spindle poison Toxicity 0.000 description 1
- 241000713675 Spumavirus Species 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 108700042077 T-Cell Receptor beta Genes Proteins 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 1
- 238000010459 TALEN Methods 0.000 description 1
- 108091008005 TRAIL–DR complexes Proteins 0.000 description 1
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
- 101710178472 Tegument protein Proteins 0.000 description 1
- 101710098841 Tegument protein UL47 Proteins 0.000 description 1
- 102100024855 Three-prime repair exonuclease 1 Human genes 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000037280 Trisomy Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
- 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 description 1
- 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 101150003160 X gene Proteins 0.000 description 1
- 241000589634 Xanthomonas Species 0.000 description 1
- GJWAPAVRQYYSTK-UHFFFAOYSA-N [(dimethyl-$l^{3}-silanyl)amino]-dimethylsilicon Chemical compound C[Si](C)N[Si](C)C GJWAPAVRQYYSTK-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- ILZCVFJUTWHERD-AYQXTPAHSA-N [[(2r,3r,4s,5r)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@@H]1F ILZCVFJUTWHERD-AYQXTPAHSA-N 0.000 description 1
- QENYANNAQSWPLM-BDXYJKHTSA-N [[(2r,3s,4r,5s)-5-(2-amino-6-sulfanylidene-3h-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QENYANNAQSWPLM-BDXYJKHTSA-N 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
- 208000010816 acute myeloblastic leukemia without maturation Diseases 0.000 description 1
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000004668 avian leukosis Diseases 0.000 description 1
- BHKICZDKIIDMNR-UHFFFAOYSA-L azane;cyclobutane-1,1-dicarboxylate;platinum(4+) Chemical compound N.N.[Pt+4].[O-]C(=O)C1(C([O-])=O)CCC1 BHKICZDKIIDMNR-UHFFFAOYSA-L 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000008970 bacterial immunity Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008275 binding mechanism Effects 0.000 description 1
- 239000002551 biofuel Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 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
- 239000006227 byproduct Substances 0.000 description 1
- 229940046731 calcineurin inhibitors Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000003710 calcium ionophore Substances 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000001876 chaperonelike Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000001767 chemoprotection Effects 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 229960000724 cidofovir Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 238000009108 consolidation therapy Methods 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 238000007822 cytometric assay Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 229940059359 dacogen Drugs 0.000 description 1
- 229960003603 decitabine Drugs 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003968 dna methyltransferase inhibitor Substances 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000002961 echo contrast media Substances 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- FSIRXIHZBIXHKT-MHTVFEQDSA-N edatrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CC(CC)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FSIRXIHZBIXHKT-MHTVFEQDSA-N 0.000 description 1
- 229950006700 edatrexate Drugs 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 230000002616 endonucleolytic effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 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
- 229960005420 etoposide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002710 external beam radiation therapy Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 229960004783 fotemustine Drugs 0.000 description 1
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000030414 genetic transfer Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000004000 hexols Chemical class 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 102000044493 human CDCA4 Human genes 0.000 description 1
- 102000045960 human DNA2 Human genes 0.000 description 1
- 102000054586 human TREX2 Human genes 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000003259 immunoinhibitory effect Effects 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 210000002602 induced regulatory T cell Anatomy 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000011419 induction treatment Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000004073 interleukin-2 production Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000000415 mammalian chromosome Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 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 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 108091062762 miR-21 stem-loop Proteins 0.000 description 1
- 108091041631 miR-21-1 stem-loop Proteins 0.000 description 1
- 108091044442 miR-21-2 stem-loop Proteins 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 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 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 108010066052 multidrug resistance-associated protein 1 Proteins 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- MRWXACSTFXYYMV-FDDDBJFASA-N nebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC=C2N=C1 MRWXACSTFXYYMV-FDDDBJFASA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229950001030 piritrexim Drugs 0.000 description 1
- 108010058237 plasma protein fraction Proteins 0.000 description 1
- 229940002993 plasmanate Drugs 0.000 description 1
- 150000003058 platinum compounds Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 108010082091 pre-T cell receptor alpha Proteins 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000008263 repair mechanism Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960003452 romidepsin Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 201000006681 severe congenital neutropenia Diseases 0.000 description 1
- 208000027390 severe congenital neutropenia 3 Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 239000005460 tetrahydrofolate Substances 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
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 208000016595 therapy related acute myeloid leukemia and myelodysplastic syndrome Diseases 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 108010036169 three prime repair exonuclease 1 Proteins 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 210000003014 totipotent stem cell Anatomy 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 230000001173 tumoral effect Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960001055 uracil mustard Drugs 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229960004528 vincristine 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
- 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
- 229960004355 vindesine Drugs 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
- GBABOYUKABKIAF-GHYRFKGUSA-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-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000012447 xenograft mouse model Methods 0.000 description 1
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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/31—Chimeric antigen receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/32—T-cell receptors [TCR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4214—Receptors for cytokines
- A61K40/4215—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4214—Receptors for cytokines
- A61K40/4217—Receptors for interleukins [IL]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
-
- 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
- C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
-
- 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
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- 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
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3061—Blood cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0081—Purging biological preparations of unwanted cells
- C12N5/0093—Purging against cancer cells
-
- 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
-
- 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
- C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6056—Antibodies
-
- 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
- A61K2039/64—Medicinal preparations containing antigens or antibodies characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
-
- 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 A61K40/00
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/21—Transmembrane domain
-
- 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 A61K40/00
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/22—Intracellular domain
-
- 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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/149—Optical investigation techniques, e.g. flow cytometry specially adapted for sorting particles, e.g. by their size or optical properties
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
- G01N2015/016—White blood cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1006—Investigating individual particles for cytology
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1028—Sorting particles
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Dispersion Chemistry (AREA)
- Pathology (AREA)
- Developmental Biology & Embryology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA201570044 | 2015-01-26 | ||
| DKPA201570044 | 2015-01-26 | ||
| PCT/EP2016/051468 WO2016120217A1 (en) | 2015-01-26 | 2016-01-25 | Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2973524A1 true CA2973524A1 (en) | 2016-08-04 |
Family
ID=52396337
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2973524A Abandoned CA2973524A1 (en) | 2015-01-26 | 2016-01-25 | Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy |
| CA2973525A Active CA2973525C (en) | 2015-01-26 | 2016-01-25 | Anti-cll1 specific single-chain chimeric antigen receptors (sccars) for cancer immunotherapy |
| CA2973532A Abandoned CA2973532A1 (en) | 2015-01-26 | 2016-01-25 | T cell receptor knock out engineered immune cells, endowed with chimeric antigen receptors binding to cd123 for the treatment of relapsed/refractory acute myeloid lymphoma or blastic plasmacytoid dendritic cell neoplasm |
| CA2973529A Abandoned CA2973529A1 (en) | 2015-01-26 | 2016-01-25 | Cll1-specific multi-chain chimeric antigen receptor |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2973525A Active CA2973525C (en) | 2015-01-26 | 2016-01-25 | Anti-cll1 specific single-chain chimeric antigen receptors (sccars) for cancer immunotherapy |
| CA2973532A Abandoned CA2973532A1 (en) | 2015-01-26 | 2016-01-25 | T cell receptor knock out engineered immune cells, endowed with chimeric antigen receptors binding to cd123 for the treatment of relapsed/refractory acute myeloid lymphoma or blastic plasmacytoid dendritic cell neoplasm |
| CA2973529A Abandoned CA2973529A1 (en) | 2015-01-26 | 2016-01-25 | Cll1-specific multi-chain chimeric antigen receptor |
Country Status (14)
| Country | Link |
|---|---|
| US (6) | US20180051089A1 (enExample) |
| EP (5) | EP3250607A1 (enExample) |
| JP (5) | JP2018504145A (enExample) |
| KR (3) | KR102329836B1 (enExample) |
| CN (5) | CN113968914A (enExample) |
| AU (5) | AU2016212162A1 (enExample) |
| BR (2) | BR112017013981A2 (enExample) |
| CA (4) | CA2973524A1 (enExample) |
| DK (2) | DK3250604T3 (enExample) |
| ES (2) | ES2842212T3 (enExample) |
| IL (3) | IL252937B (enExample) |
| MX (3) | MX2017009349A (enExample) |
| RU (3) | RU2017129455A (enExample) |
| WO (5) | WO2016120218A1 (enExample) |
Families Citing this family (165)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9950282B2 (en) | 2012-03-15 | 2018-04-24 | Flodesign Sonics, Inc. | Electronic configuration and control for acoustic standing wave generation |
| US10967298B2 (en) | 2012-03-15 | 2021-04-06 | Flodesign Sonics, Inc. | Driver and control for variable impedence load |
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| US9458450B2 (en) | 2012-03-15 | 2016-10-04 | Flodesign Sonics, Inc. | Acoustophoretic separation technology using multi-dimensional standing waves |
| US9725710B2 (en) | 2014-01-08 | 2017-08-08 | Flodesign Sonics, Inc. | Acoustophoresis device with dual acoustophoretic chamber |
| TR201910814T4 (tr) | 2014-03-19 | 2019-08-21 | Cellectis | Kanser immünoterapisi için cd123 spesifik kimerik antijen reseptörleri. |
| KR102528825B1 (ko) | 2015-04-13 | 2023-05-08 | 화이자 인코포레이티드 | B-세포 성숙 항원을 표적화하는 키메라 항원 수용체 |
| US11021699B2 (en) | 2015-04-29 | 2021-06-01 | FioDesign Sonics, Inc. | Separation using angled acoustic waves |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| US11459540B2 (en) | 2015-07-28 | 2022-10-04 | Flodesign Sonics, Inc. | Expanded bed affinity selection |
| US11474085B2 (en) | 2015-07-28 | 2022-10-18 | Flodesign Sonics, Inc. | Expanded bed affinity selection |
| BR112018002600A2 (pt) * | 2015-08-11 | 2018-10-23 | Cellectis | células para imunoterapia modificadas para direcionamento ao antígeno cd38 e para inativação do gene cd38 |
| KR20180083868A (ko) | 2015-10-30 | 2018-07-23 | 알레타 바이오쎄라퓨틱스, 인크. | 종양 형질도입용 조성물 및 방법 |
| WO2017075537A1 (en) * | 2015-10-30 | 2017-05-04 | Aleta Biotherapeutics Inc. | Compositions and methods for treatment of cancer |
| CN105331586B (zh) * | 2015-11-20 | 2020-09-15 | 上海细胞治疗研究院 | 一种包含高效杀伤启动机制的肿瘤精准t细胞及其用途 |
| CN108290955A (zh) | 2015-11-24 | 2018-07-17 | 塞勒兰特治疗公司 | 人源化抗-cll-1抗体 |
| CA3006432A1 (en) | 2015-12-04 | 2017-06-08 | Novartis Ag | Compositions and methods for immunooncology |
| EP3202783A1 (en) * | 2016-02-02 | 2017-08-09 | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Engineered antigen presenting cells 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 |
| US11104738B2 (en) | 2016-04-04 | 2021-08-31 | Hemogenyx Pharmaceuticals Llc | Monoclonal antibodies to human FLT3/FLK2 receptor protein |
| JP2019513836A (ja) | 2016-04-04 | 2019-05-30 | ヘモジェニックス リミテッド ライアビリティ カンパニー | 二重特異性抗体を使用して患者の造血幹細胞/造血前駆細胞(hsc/hp)を除去する方法 |
| US11085035B2 (en) | 2016-05-03 | 2021-08-10 | Flodesign Sonics, Inc. | Therapeutic cell washing, concentration, and separation utilizing acoustophoresis |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| IL321834A (en) | 2016-06-08 | 2025-08-01 | Precigen Inc | Cd33 specific chimeric antigen receptors |
| WO2018007263A1 (en) | 2016-07-06 | 2018-01-11 | Cellectis | Sequential gene editing in primary immune cells |
| MX2019001958A (es) * | 2016-08-19 | 2019-06-13 | Janssen Biotech Inc | Metodos para tratar la enfermedad de crohn con un anticuerpo anti-nkg2d. |
| WO2018057915A1 (en) | 2016-09-23 | 2018-03-29 | The Regents Of The University Of Michigan | Engineered lymphocytes |
| DK3757120T3 (da) | 2016-10-04 | 2022-07-25 | Prec Biosciences Inc | Co-stimulerende domæner til anvendelse i genetisk modificerede celler |
| WO2018073393A2 (en) | 2016-10-19 | 2018-04-26 | Cellectis | Tal-effector nuclease (talen) -modified allogenic cells suitable for therapy |
| WO2018073394A1 (en) | 2016-10-19 | 2018-04-26 | Cellectis | Cell death inducing chimeric antigen receptors |
| EP3529347A1 (en) | 2016-10-19 | 2019-08-28 | Flodesign Sonics, Inc. | Affinity cell extraction by acoustics |
| CN110352068A (zh) | 2016-12-02 | 2019-10-18 | 南加利福尼亚大学 | 合成的免疫受体及其使用方法 |
| WO2018115189A1 (en) | 2016-12-21 | 2018-06-28 | Cellectis | Stably enginereed proteasome inhibitor resistant immune cells for immunotherapy |
| US11236171B2 (en) | 2016-12-21 | 2022-02-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies specific for FLT3 and uses thereof |
| CN110121505B (zh) * | 2016-12-28 | 2023-08-01 | 株式会社绿十字细胞治疗 | 嵌合抗原受体和表达其的自然杀伤细胞 |
| 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 |
| JP7386082B2 (ja) | 2017-02-28 | 2023-11-24 | ブイオーアール バイオファーマ インコーポレーテッド | 系統特異的タンパク質の阻害のための組成物および方法 |
| SG11201907434RA (en) | 2017-03-22 | 2019-10-30 | Novartis Ag | Compositions and methods for immunooncology |
| CN110382542B (zh) | 2017-03-29 | 2023-06-09 | 豪夫迈·罗氏有限公司 | 针对共刺激性tnf受体的双特异性抗原结合分子 |
| AU2018246378A1 (en) * | 2017-03-31 | 2019-10-17 | Cellectis Sa | New universal chimeric antigen receptor T cells specific for CD22 |
| CA3054443A1 (en) * | 2017-04-01 | 2018-10-14 | Avm Biotechnology, Llc | Replacement of cytotoxic preconditioning before cellular immunotherapy |
| US11166985B2 (en) | 2017-05-12 | 2021-11-09 | Crispr Therapeutics Ag | Materials and methods for engineering cells and uses thereof in immuno-oncology |
| AU2018367896B2 (en) | 2017-05-12 | 2023-06-01 | Crispr Therapeutics Ag | Materials and methods for engineering cells and uses thereof in immuno-oncology |
| EP3630837A1 (en) | 2017-06-02 | 2020-04-08 | Pfizer Inc | Chimeric antigen receptors targeting flt3 |
| CA3065930A1 (en) | 2017-06-07 | 2018-12-13 | Intrexon Corporation | Expression of novel cell tags |
| JP2020524512A (ja) * | 2017-06-21 | 2020-08-20 | アイセル・ジーン・セラピューティクス・エルエルシー | キメラ抗体受容体(CARs)の組成物およびその使用方法 |
| AU2018292181B2 (en) | 2017-06-30 | 2025-04-10 | Cellectis | Cellular immunotherapy for repetitive administration |
| BR112020000492A2 (pt) * | 2017-07-09 | 2020-07-14 | Biosight Ltd. | terapia de câncer de combinação |
| EP3655440A4 (en) | 2017-07-20 | 2021-10-13 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | COMPOSITIONS AND METHODS FOR TARGETING CD33 EXPRESSING CANCERS |
| WO2019016360A1 (en) | 2017-07-21 | 2019-01-24 | Cellectis | MODIFIED IMMUNE CELLS RESISTANT TO TUMOR MICRO-ENVIRONMENT |
| CN118206655A (zh) * | 2017-07-25 | 2024-06-18 | 得克萨斯大学体系董事会 | 增强的嵌合抗原受体及其用途 |
| WO2019020733A1 (en) | 2017-07-26 | 2019-01-31 | Cellectis | METHODS OF IMMUNE CELL SELECTION OF THE ANTIGEN-DEPENDENT CHIMERIC ANTIGENIC RECEPTOR (CAR) |
| CN111629734A (zh) * | 2017-09-27 | 2020-09-04 | 南加利福尼亚大学 | 用于共刺激的新型平台、新型car设计以及过继性细胞疗法的其他增强 |
| WO2019072824A1 (en) | 2017-10-09 | 2019-04-18 | Cellectis | IMPROVED ANTI-CD123 CAR IN UNIVERSAL MODIFIED IMMUNE T LYMPHOCYTES |
| US11649294B2 (en) | 2017-11-14 | 2023-05-16 | GC Cell Corporation | Anti-HER2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same |
| EP3712178A4 (en) | 2017-11-14 | 2021-08-11 | Green Cross Lab Cell Corporation | ANTI-HER2 ANTIBODIES OR ANTIGIBODY FRAGMENT THEREOF AND CHIMERAIR ANTIGEN RECEPTOR WITH IT |
| CN109836496A (zh) * | 2017-11-25 | 2019-06-04 | 深圳宾德生物技术有限公司 | 一种靶向cd317的单链抗体、嵌合抗原受体t细胞及其制备方法和应用 |
| CN109837303A (zh) * | 2017-11-25 | 2019-06-04 | 深圳宾德生物技术有限公司 | 一种敲除pd1的靶向cd317的嵌合抗原受体t细胞及其制备方法和应用 |
| WO2019106163A1 (en) | 2017-12-01 | 2019-06-06 | Cellectis | Reprogramming of genetically engineered primary immune cells |
| KR20220066413A (ko) | 2017-12-14 | 2022-05-24 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| CN109608548A (zh) * | 2017-12-29 | 2019-04-12 | 郑州大学第附属医院 | 基于人源cd20抗体的嵌合抗原受体、慢病毒表达载体及其应用 |
| CA3086267A1 (en) | 2017-12-29 | 2019-07-04 | Cellectis | Method for improving production of car t cells |
| WO2019134001A1 (en) * | 2017-12-29 | 2019-07-04 | City Of Hope | Meditope-enabled t cells |
| WO2019129850A1 (en) | 2017-12-29 | 2019-07-04 | Cellectis | Off-the-shelf engineered cells for therapy |
| MX2020007338A (es) * | 2018-01-09 | 2020-11-06 | H Lee Moffitt Cancer Ct & Res | Composiciones y métodos para el direccionamiento a tipos de cáncer que expresan clec12a. |
| PE20211299A1 (es) | 2018-02-01 | 2021-07-20 | Pfizer | Receptores de antigeno quimericos dirigidos a cd70 |
| JP2021511811A (ja) | 2018-02-01 | 2021-05-13 | ファイザー・インク | Cd70に特異的な抗体およびその使用 |
| AR114273A1 (es) | 2018-03-02 | 2020-08-12 | Allogene Therapeutics Inc | Receptores inducibles de citoquina quimérica |
| EP3765514A1 (en) * | 2018-03-14 | 2021-01-20 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Anti-cd33 chimeric antigen receptors and their uses |
| WO2019183362A1 (en) * | 2018-03-21 | 2019-09-26 | Dana-Farber Cancer Institute, Inc. | Fc variant compositions and methods of use thereof |
| CN108530536B (zh) * | 2018-03-27 | 2021-08-13 | 刘爽 | Cart-cd123及其制备与应用 |
| CN108531457A (zh) * | 2018-04-10 | 2018-09-14 | 杭州荣泽生物科技有限公司 | 一种Cas9/RNP敲除T细胞PD-1和LAG3基因及制备CAR-T细胞的方法 |
| CA3096500A1 (en) | 2018-04-13 | 2019-10-17 | Sangamo Therapeutics France | Chimeric antigen receptor specific for interleukin-23 receptor |
| MX2020012028A (es) | 2018-05-11 | 2021-03-29 | Crispr Therapeutics Ag | Metodos y composiciones para tratar el cancer. |
| US12054558B2 (en) | 2018-05-23 | 2024-08-06 | The Jackson Laboratory | Anti-NGly-1 antibodies and methods of use |
| CN112243444A (zh) | 2018-06-08 | 2021-01-19 | 豪夫迈·罗氏有限公司 | 具有减少的翻译后修饰的肽接头 |
| US20220403001A1 (en) | 2018-06-12 | 2022-12-22 | Obsidian Therapeutics, Inc. | Pde5 derived regulatory constructs and methods of use in immunotherapy |
| WO2019246593A2 (en) * | 2018-06-22 | 2019-12-26 | Fred Hutchinson Cancer Research Center | Compositions and methods to target cll-1 and cd123 for the treatment of acute myeloid leukemia and related disorders |
| EP3817767A1 (en) * | 2018-07-02 | 2021-05-12 | Cellectis | Chimeric antigen receptors (car)-expressing cells and combination treatment for immunotherapy of patients with relapse refractory adverse genetic risk aml |
| US20210308171A1 (en) * | 2018-08-07 | 2021-10-07 | The Broad Institute, Inc. | Methods for combinatorial screening and use of therapeutic targets thereof |
| GB201813178D0 (en) * | 2018-08-13 | 2018-09-26 | Autolus Ltd | Cell |
| JP2022520138A (ja) | 2018-08-28 | 2022-03-29 | ブイオーアール バイオファーマ インコーポレーテッド | 遺伝子操作された造血幹細胞およびそれらの使用 |
| CN109503716B (zh) * | 2018-10-08 | 2021-04-27 | 浙江生研生物科技有限公司 | 一种双特异性嵌合抗原受体分子及其在肿瘤治疗上的应用 |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| KR20210089179A (ko) | 2018-10-26 | 2021-07-15 | 카파 테라퓨틱스 리미티드 | Cll1을 표적으로 하는 항체 및 이의 응용 |
| US12257286B2 (en) | 2018-10-31 | 2025-03-25 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
| US12264189B2 (en) | 2018-10-31 | 2025-04-01 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
| EP3886989A1 (en) | 2018-12-01 | 2021-10-06 | Allogene Therapeutics, Inc. | Chimeric antigen receptors targeting b-cell maturation antigen and methods of use thereof |
| SG11202104352XA (en) | 2018-12-18 | 2021-05-28 | Boehringer Ingelheim Io Canada Inc | Flt3 agonist antibodies and uses thereof |
| EP3931208A1 (en) | 2019-03-01 | 2022-01-05 | Allogene Therapeutics, Inc. | Chimeric cytokine receptors bearing a pd-1 ectodomain |
| KR20210138574A (ko) | 2019-03-01 | 2021-11-19 | 알로젠 테라퓨틱스 인코포레이티드 | Dll3 표적화 키메라 항원 수용체 및 결합제 |
| PH12021551861A1 (en) | 2019-03-01 | 2022-05-30 | Allogene Therapeutics Inc | Constitutively active chimeric cytokine receptors |
| WO2020180882A1 (en) | 2019-03-05 | 2020-09-10 | Nkarta, Inc. | Cd19-directed chimeric antigen receptors and uses thereof in immunotherapy |
| US20220152103A1 (en) * | 2019-03-11 | 2022-05-19 | Leucid Bio Ltd | MUC1 PARALLEL CAR (pCAR) THERAPEUTIC AGENTS |
| WO2020190483A1 (en) * | 2019-03-15 | 2020-09-24 | Rutgers, The State University Of New Jersey | Cd147 chimeric antigen receptors and methods of use |
| ES3036043T3 (en) | 2019-03-21 | 2025-09-12 | Allogene Therapeutics Inc | Methods for enhancing tcr alpha beta+ cell depletion efficiency |
| CN113661180B (zh) * | 2019-03-27 | 2025-08-26 | 宾夕法尼亚大学董事会 | Tn-MUC1嵌合抗原受体(CAR)T细胞疗法 |
| US20220160771A1 (en) | 2019-04-10 | 2022-05-26 | Iulia Diaconu | Flt3-specific chimeric antigen receptors and methods of using the same |
| AU2020263495B2 (en) | 2019-04-26 | 2025-09-25 | Allogene Therapeutics, Inc. | Rituximab-resistant chimeric antigen receptors and uses thereof |
| WO2020219812A1 (en) | 2019-04-26 | 2020-10-29 | Allogene Therapeutics, Inc. | Methods of manufacturing allogeneic car t cells |
| EP3962535A1 (en) | 2019-04-30 | 2022-03-09 | CRISPR Therapeutics AG | Allogeneic cell therapy of b cell malignancies using genetically engineered t cells targeting cd19 |
| JP2022538397A (ja) * | 2019-06-19 | 2022-09-02 | ユリウス-マクシミリアン-ウニヴェルシテート・ヴュルツブルク | キメラ抗原受容体設計で実施するためのウルトラモジュラー(ultramodular) IgG3ベーススペーサードメイン及び多機能部位 |
| CN112111013A (zh) * | 2019-06-22 | 2020-12-22 | 南京北恒生物科技有限公司 | 一种靶向claudin 18.2的通用型嵌合抗原受体T细胞、构建方法及其用途 |
| CA3146912A1 (en) * | 2019-07-09 | 2021-01-14 | Hemogenyx Pharmaceuticals Llc | Method of eliminating hematopoietic stem cells/hematopoietic progenitors (hsc/hp) in a patient using bi-specific antibodies |
| BR112022003553A2 (pt) | 2019-08-30 | 2022-05-24 | Allogene Therapeutics Inc | Receptores de citocina quiméricos compreendendo domínios de ligação a tgf beta |
| EP4038190A1 (en) | 2019-10-03 | 2022-08-10 | Artisan Development Labs, Inc. | Crispr systems with engineered dual guide nucleic acids |
| EP3808766A1 (en) | 2019-10-15 | 2021-04-21 | Sangamo Therapeutics France | Chimeric antigen receptor specific for interleukin-23 receptor |
| EP4081537A1 (en) | 2019-12-23 | 2022-11-02 | Cellectis | New mesothelin specific chimeric antigen receptors (car) for solid tumors cancer immunotherapy |
| TW202140533A (zh) | 2020-01-16 | 2021-11-01 | 美商異基因治療有限公司 | 靶向B 細胞成熟抗原之嵌合抗原受體及γ 分泌酵素抑制劑之組合療法 |
| CN115175929A (zh) | 2020-02-24 | 2022-10-11 | 艾洛基治疗公司 | 活性增强的bcma car-t细胞 |
| JP2023517011A (ja) | 2020-03-05 | 2023-04-21 | ネオティーエックス セラピューティクス リミテッド | 免疫細胞を用いて癌を治療するための方法および組成物 |
| AU2021231887A1 (en) * | 2020-03-06 | 2022-10-20 | Purdue Research Foundation | Methods, compounds, and compositions for modifying CAR-T cell activity |
| US20230212319A1 (en) | 2020-03-16 | 2023-07-06 | University Of Southern California | Novel antigen binding domains and synthetic antigen receptors incorporating the same |
| MX2022011335A (es) * | 2020-03-18 | 2022-10-07 | Kindred Biosciences Inc | Anticuerpos del receptor anti-interleucina 4 para uso veterinario. |
| AU2021239360A1 (en) | 2020-03-20 | 2022-11-10 | Lyell Immunopharma, Inc. | Novel recombinant cell surface markers |
| KR20230006477A (ko) * | 2020-03-27 | 2023-01-10 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | Hsp70을 표적화하는 모노클로날 항체 및 이의 치료학적 용도 |
| CN115803435A (zh) | 2020-05-06 | 2023-03-14 | 塞勒克提斯公司 | 用于在细胞基因组中靶向插入外源序列的方法 |
| US20230227525A1 (en) * | 2020-05-08 | 2023-07-20 | Smt Bio Co., Ltd. | Chimeric antigen receptor for treatment of cancer |
| GB202007842D0 (en) * | 2020-05-26 | 2020-07-08 | Quell Therapeutics Ltd | Polypeptide useful in adoptive cell therapy |
| CN113735973B (zh) * | 2020-05-28 | 2023-05-09 | 中国科学院微生物研究所 | 一种抗SIRPα抗体及其应用 |
| US20230220104A1 (en) * | 2020-05-29 | 2023-07-13 | Brightpath Biotherapeutics Co., Ltd. | Anti-cd73 antibody and use thereof |
| EP4176261A1 (en) | 2020-07-03 | 2023-05-10 | Cellectis S.A. | Method for determining potency of chimeric antigen receptor expressing immune cells |
| WO2022020456A2 (en) | 2020-07-21 | 2022-01-27 | Allogene Therapeutics, Inc. | Chimeric antigen receptors with enhanced signaling and activities and uses thereof |
| EP4185616A1 (en) | 2020-07-24 | 2023-05-31 | Cellectis S.A. | T-cells expressing immune cell engagers in allogenic settings |
| JP2023537048A (ja) * | 2020-08-07 | 2023-08-30 | ネオジン セラピューティクス ビー.ブイ. | 遺伝子改変したt細胞の濃縮方法 |
| CN112079927B (zh) * | 2020-09-18 | 2021-12-28 | 西安桑尼赛尔生物医药有限公司 | 一种cd123结合蛋白、含其的car及其应用 |
| WO2022061837A1 (en) * | 2020-09-27 | 2022-03-31 | Jiangsu Cell Tech Medical Research Institute Co., Ltd. | Fibronectin extra domain b (edb) -specific car-t for cancer |
| CN113234169B (zh) * | 2020-12-11 | 2022-11-01 | 广州百暨基因科技有限公司 | 靶向cll1嵌合抗原受体及其应用 |
| CN113980134B (zh) * | 2020-12-11 | 2022-05-31 | 广州百暨基因科技有限公司 | 抗cll1抗体及其应用 |
| CN113248622B (zh) * | 2020-12-11 | 2022-11-01 | 广州百暨基因科技有限公司 | 一种靶向cll1和nkg2d配体的双靶点嵌合抗原受体及其应用 |
| US20220184124A1 (en) | 2020-12-14 | 2022-06-16 | Allogene Therapeutics, Inc. | Methods and reagents for characterizing car t cells for therapies |
| JP2024500847A (ja) | 2020-12-18 | 2024-01-10 | センチュリー セラピューティクス,インコーポレイテッド | 適合可能な受容体特異性を有するキメラ抗原受容体システム |
| MX2023007384A (es) | 2020-12-21 | 2023-07-05 | Allogene Therapeutics Inc | Car con puerta cd45 activado por proteasa. |
| AU2021414400A1 (en) | 2020-12-31 | 2023-08-17 | Innate Pharma | Multifunctional natural killer (nk) cell engagers binding to nkp46 and cd123 |
| CN112694532B (zh) * | 2021-01-12 | 2023-04-18 | 倍而达药业(苏州)有限公司 | 抗Siglec-15的抗体或其抗原结合片段及应用 |
| CN112661816B (zh) * | 2021-01-13 | 2022-10-11 | 江西省人民医院 | 用于利妥昔单抗血药浓度检测的人工抗原及试剂盒 |
| KR20230135593A (ko) | 2021-01-28 | 2023-09-25 | 알로젠 테라퓨틱스 인코포레이티드 | 면역 세포를 형질도입하는 방법 |
| US20220251505A1 (en) | 2021-01-29 | 2022-08-11 | Allogene Therapeutics, Inc. | KNOCKDOWN OR KNOCKOUT OF ONE OR MORE OF TAP2, NLRC5, B2m, TRAC, RFX5, RFXAP and RFXANK TO MITIGATE T CELL RECOGNITION OF ALLOGENEIC CELL PRODUCTS |
| WO2022182801A1 (en) | 2021-02-25 | 2022-09-01 | Artisan Development Labs, Inc. | Compositions and methods for targeting, editing, or modifying genes |
| AU2022227686A1 (en) | 2021-02-25 | 2023-07-27 | Lyell Immunopharma, Inc. | Ror1 targeting chimeric antigen receptor |
| CA3216563A1 (en) * | 2021-04-30 | 2022-11-03 | Beatriz Aranda-Orgilles | New anti-muc1 cars and gene edited immune cells for solid tumors cancer immunotherapy |
| WO2022256448A2 (en) | 2021-06-01 | 2022-12-08 | Artisan Development Labs, Inc. | Compositions and methods for targeting, editing, or modifying genes |
| WO2022266075A1 (en) | 2021-06-14 | 2022-12-22 | Caribou Biosciences, Inc. | Methods and materials for treating cancer using car constructs with an intracellular domain comprising a stap domain and a kinase domain or a stap domain and a phosphatase domain |
| KR20240021826A (ko) | 2021-06-15 | 2024-02-19 | 알로젠 테라퓨틱스 인코포레이티드 | 동종이계 car t 세포 지속성을 연장시키기 위한 숙주 cd70+ 동종반응성 세포의 선택적 표적화 |
| CN115477705B (zh) * | 2021-06-16 | 2024-02-23 | 四川大学华西医院 | 一种基于颗粒酶b构建的嵌合抗原受体免疫细胞制备及其应用 |
| CN115477704B (zh) * | 2021-06-16 | 2024-02-23 | 四川大学华西医院 | 一种基于lox1构建的嵌合抗原受体免疫细胞制备及其应用 |
| US20250034558A1 (en) | 2021-06-18 | 2025-01-30 | Artisan Development Labs, Inc. | Compositions and methods for targeting, editing or modifying human genes |
| WO2023020471A1 (en) * | 2021-08-16 | 2023-02-23 | Utc Therapeutics (Shanghai) Co., Ltd. | Cd123-targetting antibodies and uses thereof in cancer therapies |
| MX2024002590A (es) | 2021-09-01 | 2024-03-22 | Springworks Therapeutics Inc | Sintesis de nirogacestat. |
| WO2023125289A1 (zh) * | 2021-12-31 | 2023-07-06 | 上海宏成药业有限公司 | 抗pd-1抗体及其用途 |
| US20250388896A1 (en) | 2022-03-01 | 2025-12-25 | Celyntra Therapeutics Sa | Composition and methods for transgene insertion |
| US20230346934A1 (en) | 2022-03-29 | 2023-11-02 | Allogene Therapeutics, Inc. | Chimeric switch receptors for the conversion of immunesuppressive signals to costimulatory signals |
| CN119487069A (zh) | 2022-04-11 | 2025-02-18 | Vor生物制药股份有限公司 | 结合剂及其使用方法 |
| JP7747911B2 (ja) | 2022-05-27 | 2025-10-01 | サノフイ | NKp46に結合するナチュラルキラー(NK)細胞エンゲージャー及びFCエンジニアリングを有するBCMA変異体 |
| US20240042030A1 (en) | 2022-07-29 | 2024-02-08 | Allogene Therapeutics, Inc. | Engineered cells with reduced gene expression to mitigate immune cell recognition |
| WO2024051751A1 (zh) * | 2022-09-06 | 2024-03-14 | 河北森朗生物科技有限公司 | 抗cd123的纳米抗体、嵌合抗原受体及其应用 |
| EP4590337A1 (en) * | 2022-09-20 | 2025-07-30 | Dana-Farber Cancer Institute, Inc. | Receptor-mediated endocytosis for targeted internalization and degradation of membrane proteins and cargos |
| CN118240086B (zh) * | 2022-10-08 | 2025-05-09 | 东莞市朋志生物科技有限公司 | 抗纤维蛋白降解产物抗体、检测纤维蛋白降解产物的试剂和试剂盒 |
| TW202440623A (zh) | 2022-11-28 | 2024-10-16 | 美商艾洛基因醫療公司 | 靶向密連蛋白18﹒2之嵌合抗原受體及結合劑以及其用途 |
| WO2024121385A1 (en) | 2022-12-09 | 2024-06-13 | Cellectis S.A. | Two-dose regimen in immunotherapy |
| WO2024238565A1 (en) | 2023-05-15 | 2024-11-21 | Vor Biopharma Inc. | Egf-like module containing mucin-like hormone-like 2 (erm2) binding agents and methods of use thereof |
| CN117783521B (zh) * | 2023-11-23 | 2025-03-04 | 中国农业科学院兰州兽医研究所 | 检测非洲猪瘟病毒p30蛋白抗体的竞争ELISA试剂盒 |
| CN117964761B (zh) * | 2023-12-21 | 2025-04-01 | 华润生物医药有限公司 | 抗trem2抗体及其用途 |
| WO2025233825A1 (en) * | 2024-05-06 | 2025-11-13 | Janssen Pharmaceutica Nv | Enrichment of cells expressing a bird linker |
Family Cites Families (128)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| 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 |
| GB8611832D0 (en) | 1986-05-15 | 1986-06-25 | Holland I B | Polypeptide |
| US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
| US5037743A (en) | 1988-08-05 | 1991-08-06 | Zymogenetics, Inc. | BAR1 secretion signal |
| US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
| 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 |
| 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 |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US20030229208A1 (en) | 1988-12-28 | 2003-12-11 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| WO1992022653A1 (en) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| ES2202310T3 (es) | 1991-12-13 | 2004-04-01 | Xoma Corporation | Metodos y materiales para la preparacion de dominios variables de anticuerpos modificados y sus usos terapeuticos. |
| GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| AU6704794A (en) | 1993-04-13 | 1994-11-08 | Sloan-Kettering Institute For Cancer Research | Protection of human bone marrow from high dose antifolate therapy using mutated human dihydrofolate reductase dna |
| US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
| 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 |
| US6010613A (en) | 1995-12-08 | 2000-01-04 | Cyto Pulse Sciences, Inc. | Method of treating materials with pulsed electrical fields |
| WO1997033988A1 (en) | 1996-03-12 | 1997-09-18 | Sloan-Kettering Institute For Cancer Research | Double mutants of dihydrofolate reductase and methods of using same |
| ES2302726T3 (es) | 2000-02-24 | 2008-08-01 | Invitrogen Corporation | Estimulacion y concentracion simultanea de celulas. |
| US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
| US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| EP1319023B8 (en) | 2000-09-13 | 2009-07-15 | multimmune GmbH | An hsp70 peptide stimulating natural killer (nk) cell activity and uses thereof |
| AU2001297703B2 (en) | 2000-11-07 | 2006-10-19 | City Of Hope | CD19-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 |
| US7514537B2 (en) | 2001-04-30 | 2009-04-07 | City Of Hope | Chimeric immunoreceptor useful in treating human gliomas |
| US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| SI1578446T1 (sl) | 2002-11-07 | 2015-07-31 | Immunogen, Inc. | Protitelesa proti-cd33 in metoda za zdravljenje akutne mieloidne levkemije z uporabo istega |
| BRPI0316779B1 (pt) * | 2002-12-16 | 2020-04-28 | Genentech Inc | anticorpo humanizado que liga cd20 humano, composição, artigo manufaturado, método de indução da apoptose, método de tratamento de câncer cd20 positivo, métodos de tratamento de doenças autoimunes, ácidos nucléicos isolados, vetores de expressão, células hospedeiras, método para a produção de um anticorpo 2h7 humanizado, polipeptídeo isolado, formulação líquida, método de tratamento de artrite reumatóide (ra) e anticorpos de ligação de cd20 humanizados |
| CN1826408B (zh) | 2003-03-14 | 2011-01-26 | 塞托·帕尔斯科技公司 | 大容量离体电穿孔法 |
| WO2005000894A2 (en) * | 2003-06-25 | 2005-01-06 | Crucell Holland B.V. | Binding molecules for the treatment of myeloid cell malignancies |
| EP1638510B1 (en) | 2003-07-01 | 2015-09-02 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
| ES2458636T3 (es) | 2003-08-18 | 2014-05-06 | Medimmune, Llc | Humanización de anticuerpos |
| AU2004280333A1 (en) | 2003-08-22 | 2005-04-21 | Medimmune, Llc | Humanization of antibodies |
| 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 |
| US20130266551A1 (en) | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
| WO2005054295A2 (en) | 2003-12-05 | 2005-06-16 | Multimmune Gmbh | Therapeutic and diagnostic anti-hsp 70 antibodies |
| CA2555503C (en) * | 2004-02-16 | 2018-03-27 | Micromet Ag | Humanized anti-cd3 bispecific binding molecules having reduced immunogenicity, uses and compositions relating thereto |
| 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 |
| GB0505971D0 (en) | 2005-03-23 | 2005-04-27 | Isis Innovation | Delivery of molecules to a lipid bilayer |
| NZ612578A (en) | 2005-08-19 | 2014-11-28 | Abbvie Inc | Dual variable domain immunoglobin and uses thereof |
| US9078843B2 (en) * | 2005-09-22 | 2015-07-14 | Irun R. Cohen | Immunogenic fragments of T-cell receptor constant domains and peptides derived therefrom |
| WO2008102120A1 (en) | 2007-02-20 | 2008-08-28 | Oxford Nanopore Technologies Limited | Lipid bilayer sensor system |
| EP2537416B1 (en) | 2007-03-30 | 2014-11-12 | Memorial Sloan-Kettering Cancer Center | Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes |
| WO2009051974A1 (en) * | 2007-10-17 | 2009-04-23 | Nuvelo, Inc. | Antibodes to cll-1 |
| EP2072527A1 (en) * | 2007-12-21 | 2009-06-24 | Altonabiotec AG | Fusion polypeptides comprising a SHBG dimerization component and uses thereof |
| 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) |
| US8822647B2 (en) | 2008-08-26 | 2014-09-02 | City Of Hope | Method and compositions using a chimeric antigen receptor for enhanced anti-tumor effector functioning of T cells |
| DE102009045006A1 (de) | 2009-09-25 | 2011-04-14 | Technische Universität Dresden | Anti-CD33 Antikörper und ihre Anwendung zum Immunotargeting bei der Behandlung von CD33-assoziierten Erkrankungen |
| US8956828B2 (en) * | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| EP2332994A1 (en) * | 2009-12-09 | 2011-06-15 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Trispecific therapeutics against acute myeloid leukaemia |
| US20130022629A1 (en) * | 2010-01-04 | 2013-01-24 | Sharpe Arlene H | Modulators of Immunoinhibitory Receptor PD-1, and Methods of Use Thereof |
| US9487800B2 (en) | 2010-09-08 | 2016-11-08 | Chemotherapeutisches Forschunginstitut Georg-Speyer-Haus | Interleukin 15 as selectable marker for gene transfer in lymphocytes |
| EP2614077B1 (en) | 2010-09-08 | 2016-08-17 | Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus | Chimeric antigen receptors with an optimized hinge region |
| WO2012050374A2 (en) | 2010-10-13 | 2012-04-19 | Innocell, Inc. | Immunotherapy for solid tumors |
| AU2011319725A1 (en) | 2010-10-27 | 2013-05-30 | Cellectis | Method for increasing the efficiency of double-strand break-induced mutagenesis |
| SG10201600656WA (en) * | 2010-10-27 | 2016-02-26 | Baxter Int | FVIII Peptides For Immune Tolerance Induction And Immunodiagnostics |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| CN103442768A (zh) | 2011-01-18 | 2013-12-11 | 宾夕法尼亚大学董事会 | 治疗癌的组合物和方法 |
| CN103635486B (zh) | 2011-02-11 | 2017-05-17 | 纪念斯隆-凯特琳癌症中心 | Hla限制性、肽特异性的抗原结合蛋白 |
| US8968539B2 (en) | 2011-03-08 | 2015-03-03 | Electronic Biosciences, Inc. | Methods for voltage-induced protein incorporation into planar lipid bilayers |
| BR112013024395B1 (pt) * | 2011-03-23 | 2021-10-26 | Fred Hutchinson Cancer Research Center | Composições adotivas de imunoterapia celular e método para fabricação da dita composição |
| WO2012134975A1 (en) | 2011-03-28 | 2012-10-04 | St. Jude Children's Research Hospital | Methods and compositions employing immunogenic fusion proteins |
| SG10201602651YA (en) | 2011-04-05 | 2016-05-30 | Cellectis | Method for the generation of compact tale-nucleases and uses thereof |
| CN107188969B (zh) | 2011-04-08 | 2021-08-27 | 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 |
| US9285592B2 (en) | 2011-08-18 | 2016-03-15 | Google Inc. | Wearable device with input and output structures |
| SG11201400527XA (en) | 2011-09-16 | 2014-04-28 | Univ Pennsylvania | Rna engineered t cells for the treatment of cancer |
| WO2013051718A1 (ja) | 2011-10-07 | 2013-04-11 | 国立大学法人三重大学 | キメラ抗原受容体 |
| CA3101452C (en) * | 2011-10-10 | 2024-04-23 | City Of Hope | Meditopes and meditope-binding antibodies and uses thereof |
| AU2012325915A1 (en) | 2011-10-20 | 2014-04-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-CD22 chimeric antigen receptors |
| US9422351B2 (en) | 2011-11-03 | 2016-08-23 | The Trustees Of The University Of Pennsylvania | Isolated B7-H4 specific compositions and methods of use thereof |
| WO2013070468A1 (en) | 2011-11-08 | 2013-05-16 | The Trustees Of The University Of Pennsylvania | Glypican-3-specific antibody and uses thereof |
| KR102134326B1 (ko) * | 2011-11-15 | 2020-07-17 | 더 월터 앤드 엘리자 홀 인스티튜트 오브 메디컬 리서치 | 가용성 매개자 |
| US10391126B2 (en) | 2011-11-18 | 2019-08-27 | Board Of Regents, The University Of Texas System | CAR+ T cells genetically modified to eliminate expression of T-cell receptor and/or HLA |
| AU2013221672B2 (en) | 2012-02-13 | 2017-11-09 | Seattle Children's Hospital D/B/A Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
| 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 |
| AU2013222288A1 (en) | 2012-02-22 | 2014-08-14 | The Trustees Of The University Of Pennsylvania | Use of ICOS-based CARs to enhance antitumor activity and CAR persistence |
| US10040846B2 (en) * | 2012-02-22 | 2018-08-07 | The Trustees Of The University Of Pennsylvania | Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer |
| WO2013126726A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Double transgenic t cells comprising a car and a tcr and their methods of use |
| HK1203393A1 (en) * | 2012-04-11 | 2015-10-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptors targeting b-cell maturation antigen |
| GB201206559D0 (en) | 2012-04-13 | 2012-05-30 | Ucl Business Plc | Polypeptide |
| US9163090B2 (en) * | 2012-05-07 | 2015-10-20 | Cellerant Therapeutics, Inc. | Antibodies specific for CLL-1 |
| US20130309223A1 (en) | 2012-05-18 | 2013-11-21 | Seattle Genetics, Inc. | CD33 Antibodies And Use Of Same To Treat Cancer |
| US20150017136A1 (en) | 2013-07-15 | 2015-01-15 | Cellectis | Methods for engineering allogeneic and highly active t cell for immunotherapy |
| KR102247979B1 (ko) | 2012-05-25 | 2021-05-04 | 셀렉티스 | 면역요법을 위한 동종이형 및 면역억제제 저항성인 t 세포의 조작 방법 |
| CN103483452B (zh) * | 2012-06-12 | 2021-08-13 | 上海细胞治疗集团有限公司 | 双信号独立的嵌合抗原受体及其用途 |
| MX2015000426A (es) | 2012-07-13 | 2015-07-14 | Univ Pennsylvania | Incremento de actividad de celulas t car mediante cointroduccion de un anticuerpo biespecifico. |
| CA2878856A1 (en) | 2012-07-13 | 2014-01-16 | The Trustees Of The University Of Pennsylvania | Compositions and methods for regulating car t cells |
| CN104769103B (zh) * | 2012-09-04 | 2018-06-08 | 塞勒克提斯公司 | 多链嵌合抗原受体和其用途 |
| AU2013204922B2 (en) | 2012-12-20 | 2015-05-14 | Celgene Corporation | Chimeric antigen receptors |
| US9573988B2 (en) * | 2013-02-20 | 2017-02-21 | Novartis Ag | Effective targeting of primary human leukemia using anti-CD123 chimeric antigen receptor engineered T cells |
| HK1217000A1 (zh) | 2013-03-14 | 2016-12-16 | Bellicum Pharmaceuticals, Inc. | 控制t细胞增殖的方法 |
| WO2014145252A2 (en) * | 2013-03-15 | 2014-09-18 | Milone Michael C | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
| CA2907397C (en) | 2013-03-15 | 2022-11-22 | Anthrogenesis Corporation | Modified t lymphocytes |
| US9657105B2 (en) * | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
| TWI654206B (zh) | 2013-03-16 | 2019-03-21 | 諾華公司 | 使用人類化抗-cd19嵌合抗原受體治療癌症 |
| MY172897A (en) | 2013-05-13 | 2019-12-13 | Cellectis | Cd19 specific chimeric antigen receptor and uses thereof |
| AU2014266833B2 (en) | 2013-05-13 | 2020-07-02 | Cellectis | Methods for engineering highly active T cell for immunotherapy |
| EP3004337B1 (en) * | 2013-05-29 | 2017-08-02 | Cellectis | Methods for engineering t cells for immunotherapy by using rna-guided cas nuclease system |
| ES2883131T3 (es) | 2013-05-29 | 2021-12-07 | Cellectis | Métodos para la modificación de células T para inmunoterapia utilizando el sistema de nucleasa CAS guiado por ARN |
| CA2912389C (en) * | 2013-06-10 | 2020-01-28 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for reducing immunosupression by tumor cells |
| GB201317929D0 (en) | 2013-10-10 | 2013-11-27 | Ucl Business Plc | Chimeric antigen receptor |
| PL3071222T3 (pl) | 2013-11-21 | 2021-04-19 | Ucl Business Ltd | Komórka |
| AU2014351797B2 (en) | 2013-11-22 | 2021-03-11 | Cellectis | Method of engineering chemotherapy drug resistant T-cells for immunotherapy |
| JP2017504601A (ja) | 2013-12-20 | 2017-02-09 | セレクティスCellectis | 免疫療法のためにマルチインプットシグナル感受性t細胞を操作する方法 |
| HRP20201906T1 (hr) * | 2013-12-20 | 2021-04-02 | Fred Hutchinson Cancer Research Center | Označene kimerne efektorske molekule i njihovi receptori |
| TR201819571T4 (tr) | 2014-02-14 | 2019-01-21 | Cellectis | Hem immün hücrelerde hem de patolojik hücrelerde bulunan antijenleri hedef almak amacıyla değiştirilmiş immünoterapiye yönelik hücreler. |
| AU2015218396A1 (en) | 2014-02-14 | 2016-08-11 | Bellicum Pharmaceuticals, Inc. | Methods for activating T cells using an inducible chimeric polypeptide |
| ES2782125T3 (es) | 2014-03-11 | 2020-09-10 | Cellectis | Método para generar linfocitos T compatibles para trasplante alogénico |
| ES2939760T3 (es) | 2014-03-15 | 2023-04-26 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico para antígenos |
| TR201910814T4 (tr) * | 2014-03-19 | 2019-08-21 | Cellectis | Kanser immünoterapisi için cd123 spesifik kimerik antijen reseptörleri. |
| CA2945620C (en) * | 2014-04-14 | 2022-12-06 | Cellectis | Bcma (cd269) specific chimeric antigen receptors for cancer immunotherapy |
| CN107109420A (zh) * | 2014-07-21 | 2017-08-29 | 诺华股份有限公司 | 使用cll-1嵌合抗原受体的癌症治疗 |
| KR102612313B1 (ko) | 2014-07-21 | 2023-12-12 | 노파르티스 아게 | 인간화 항-bcma 키메라 항원 수용체를 사용한 암의 치료 |
| ES2688035T3 (es) * | 2014-08-29 | 2018-10-30 | Gemoab Monoclonals Gmbh | Receptor de antígeno universal que expresa células inmunes para direccionamiento de antígenos múltiples diversos, procedimiento para fabricación del mismo y utilización del mismo para tratamiento de cáncer, infecciones y enfermedades autoinmunes |
| JP7098325B2 (ja) | 2014-12-05 | 2022-07-11 | シティ・オブ・ホープ | Cs1標的化キメラ抗原レセプター改変t細胞 |
| KR102528825B1 (ko) | 2015-04-13 | 2023-05-08 | 화이자 인코포레이티드 | B-세포 성숙 항원을 표적화하는 키메라 항원 수용체 |
| US9668192B2 (en) | 2015-10-12 | 2017-05-30 | Telefonaktiebolaget Lm Ericsson (Publ) | Cell boundary crossing in a unidirectional SFN for high speed trains |
-
2016
- 2016-01-25 JP JP2017557491A patent/JP2018504145A/ja active Pending
- 2016-01-25 US US15/546,623 patent/US20180051089A1/en not_active Abandoned
- 2016-01-25 ES ES16703450T patent/ES2842212T3/es active Active
- 2016-01-25 US US15/546,633 patent/US11014989B2/en active Active
- 2016-01-25 RU RU2017129455A patent/RU2017129455A/ru not_active Application Discontinuation
- 2016-01-25 KR KR1020177021615A patent/KR102329836B1/ko active Active
- 2016-01-25 CA CA2973524A patent/CA2973524A1/en not_active Abandoned
- 2016-01-25 CN CN202111328553.6A patent/CN113968914A/zh active Pending
- 2016-01-25 US US15/546,604 patent/US20180000914A1/en not_active Abandoned
- 2016-01-25 EP EP16704136.7A patent/EP3250607A1/en not_active Withdrawn
- 2016-01-25 CN CN201680006992.6A patent/CN107531801B/zh active Active
- 2016-01-25 CN CN202111329158.XA patent/CN113968915A/zh active Pending
- 2016-01-25 DK DK16703448.7T patent/DK3250604T3/da active
- 2016-01-25 AU AU2016212162A patent/AU2016212162A1/en not_active Abandoned
- 2016-01-25 CN CN201680006972.9A patent/CN107406516B/zh active Active
- 2016-01-25 AU AU2016212159A patent/AU2016212159A1/en not_active Abandoned
- 2016-01-25 CN CN201680006922.0A patent/CN107438618A/zh active Pending
- 2016-01-25 RU RU2017129591A patent/RU2732925C2/ru active
- 2016-01-25 BR BR112017013981-2A patent/BR112017013981A2/pt active Search and Examination
- 2016-01-25 EP EP16701616.1A patent/EP3250602A1/en not_active Withdrawn
- 2016-01-25 CA CA2973525A patent/CA2973525C/en active Active
- 2016-01-25 EP EP16703448.7A patent/EP3250604B1/en active Active
- 2016-01-25 KR KR1020177023447A patent/KR102661969B1/ko active Active
- 2016-01-25 JP JP2017557489A patent/JP6779909B2/ja active Active
- 2016-01-25 MX MX2017009349A patent/MX2017009349A/es unknown
- 2016-01-25 EP EP16703449.5A patent/EP3250605A1/en not_active Ceased
- 2016-01-25 WO PCT/EP2016/051469 patent/WO2016120218A1/en not_active Ceased
- 2016-01-25 WO PCT/EP2016/051467 patent/WO2016120216A1/en not_active Ceased
- 2016-01-25 WO PCT/EP2016/051468 patent/WO2016120217A1/en not_active Ceased
- 2016-01-25 JP JP2017557490A patent/JP2018504144A/ja not_active Withdrawn
- 2016-01-25 MX MX2017009182A patent/MX389057B/es unknown
- 2016-01-25 BR BR112017015453-6A patent/BR112017015453A2/pt not_active Application Discontinuation
- 2016-01-25 AU AU2016212158A patent/AU2016212158B2/en active Active
- 2016-01-25 WO PCT/EP2016/051470 patent/WO2016120219A1/en not_active Ceased
- 2016-01-25 KR KR1020177023078A patent/KR20170135824A/ko not_active Withdrawn
- 2016-01-25 EP EP16703450.3A patent/EP3250606B1/en active Active
- 2016-01-25 CA CA2973532A patent/CA2973532A1/en not_active Abandoned
- 2016-01-25 WO PCT/EP2016/051471 patent/WO2016120220A1/en not_active Ceased
- 2016-01-25 US US15/546,630 patent/US20180002435A1/en not_active Abandoned
- 2016-01-25 AU AU2016212160A patent/AU2016212160B2/en active Active
- 2016-01-25 JP JP2017557488A patent/JP2018504143A/ja active Pending
- 2016-01-25 MX MX2017009181A patent/MX381908B/es unknown
- 2016-01-25 JP JP2017557487A patent/JP6884709B2/ja active Active
- 2016-01-25 AU AU2016212161A patent/AU2016212161A1/en not_active Abandoned
- 2016-01-25 CA CA2973529A patent/CA2973529A1/en not_active Abandoned
- 2016-01-25 US US15/546,619 patent/US20180002427A1/en not_active Abandoned
- 2016-01-25 RU RU2017129592A patent/RU2731543C2/ru active
- 2016-01-25 ES ES16703448T patent/ES2869972T3/es active Active
- 2016-01-25 DK DK16703450.3T patent/DK3250606T3/da active
-
2017
- 2017-06-15 IL IL252937A patent/IL252937B/en unknown
- 2017-06-19 IL IL253012A patent/IL253012A0/en unknown
- 2017-06-20 IL IL253049A patent/IL253049B/en unknown
-
2023
- 2023-10-05 US US18/481,797 patent/US20240228636A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2016212160B2 (en) | Anti-CLL1 specific single-chain Chimeric Antigen Receptors (scCARs) for cancer immunotherapy | |
| US11498971B2 (en) | BCMA (CD269) specific chimeric antigen receptors for cancer immunotherapy | |
| US20210163612A1 (en) | Cd123 specific chimeric antigen receptors for cancer immunotherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220419 |
|
| FZDE | Discontinued |
Effective date: 20220419 |