CA2949325A1 - Cd123 specific multi-chain chimeric antigen receptor - Google Patents
Cd123 specific multi-chain chimeric antigen receptor Download PDFInfo
- Publication number
- CA2949325A1 CA2949325A1 CA2949325A CA2949325A CA2949325A1 CA 2949325 A1 CA2949325 A1 CA 2949325A1 CA 2949325 A CA2949325 A CA 2949325A CA 2949325 A CA2949325 A CA 2949325A CA 2949325 A1 CA2949325 A1 CA 2949325A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- chain
- cells
- cell
- 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 226
- 210000004027 cell Anatomy 0.000 claims abstract description 236
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 claims abstract description 146
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 145
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 136
- 229920001184 polypeptide Polymers 0.000 claims abstract description 131
- 210000002865 immune cell Anatomy 0.000 claims abstract description 58
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 42
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 42
- 239000002157 polynucleotide Substances 0.000 claims abstract description 42
- 239000013598 vector Substances 0.000 claims abstract description 20
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 104
- 238000000034 method Methods 0.000 claims description 49
- 108020001756 ligand binding domains Proteins 0.000 claims description 42
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 31
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 31
- 230000002463 transducing effect Effects 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 20
- 108090000623 proteins and genes Proteins 0.000 claims description 20
- 239000003446 ligand Substances 0.000 claims description 19
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 17
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 17
- 150000007523 nucleic acids Chemical group 0.000 claims description 17
- 150000001413 amino acids Chemical group 0.000 claims description 15
- 239000012634 fragment Substances 0.000 claims description 15
- 230000001086 cytosolic effect Effects 0.000 claims description 14
- 230000004913 activation Effects 0.000 claims description 13
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 12
- -1 ICOS Proteins 0.000 claims description 11
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 11
- 230000000139 costimulatory effect Effects 0.000 claims description 11
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 102000009438 IgE Receptors Human genes 0.000 claims description 9
- 108010073816 IgE Receptors Proteins 0.000 claims description 9
- 101150013553 CD40 gene Proteins 0.000 claims description 7
- 102100035793 CD83 antigen Human genes 0.000 claims description 7
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 claims description 7
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 7
- 102100027207 CD27 antigen Human genes 0.000 claims description 6
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 6
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 claims description 6
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 6
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 claims description 6
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 6
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 5
- 108010065816 zeta chain antigen T cell receptor Proteins 0.000 claims description 4
- 230000001472 cytotoxic effect Effects 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 210000000822 natural killer cell Anatomy 0.000 claims description 2
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 38
- 239000000427 antigen Substances 0.000 abstract description 20
- 108091007433 antigens Proteins 0.000 abstract description 20
- 102000036639 antigens Human genes 0.000 abstract description 20
- 201000011510 cancer Diseases 0.000 abstract description 17
- 238000009169 immunotherapy Methods 0.000 abstract description 12
- 230000003211 malignant effect Effects 0.000 abstract description 12
- 102000005962 receptors Human genes 0.000 abstract description 12
- 108020003175 receptors Proteins 0.000 abstract description 12
- 208000032839 leukemia Diseases 0.000 abstract description 11
- 230000019491 signal transduction Effects 0.000 abstract description 9
- 230000009257 reactivity Effects 0.000 abstract description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 45
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 41
- 102100038006 High affinity immunoglobulin epsilon receptor subunit alpha Human genes 0.000 description 39
- 108050001540 High affinity immunoglobulin epsilon receptor subunit beta Proteins 0.000 description 39
- 238000011282 treatment Methods 0.000 description 28
- 241000282414 Homo sapiens Species 0.000 description 23
- 125000003275 alpha amino acid group Chemical group 0.000 description 20
- 108020004999 messenger RNA Proteins 0.000 description 20
- 230000000694 effects Effects 0.000 description 16
- 238000004520 electroporation Methods 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 13
- 230000011664 signaling Effects 0.000 description 13
- 208000009329 Graft vs Host Disease Diseases 0.000 description 12
- 208000024908 graft versus host disease Diseases 0.000 description 12
- 230000008685 targeting Effects 0.000 description 12
- 108091008874 T cell receptors Proteins 0.000 description 11
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 11
- 238000000684 flow cytometry Methods 0.000 description 11
- 108020004705 Codon Proteins 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 8
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 8
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 8
- 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 8
- 108010033174 Deoxycytidine kinase Proteins 0.000 description 8
- 102100029588 Deoxycytidine kinase Human genes 0.000 description 8
- 108010087819 Fc receptors Proteins 0.000 description 8
- 102000009109 Fc receptors Human genes 0.000 description 8
- 101100508818 Mus musculus Inpp5k gene Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 description 8
- 101100366438 Rattus norvegicus Sphkap gene Proteins 0.000 description 8
- 229960000390 fludarabine Drugs 0.000 description 8
- 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 8
- 238000010361 transduction Methods 0.000 description 8
- 230000026683 transduction Effects 0.000 description 8
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 7
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 210000000349 chromosome Anatomy 0.000 description 7
- 238000003501 co-culture Methods 0.000 description 7
- 229960000684 cytarabine Drugs 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 210000003705 ribosome Anatomy 0.000 description 7
- 230000003248 secreting effect Effects 0.000 description 7
- 210000000130 stem cell Anatomy 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 230000005945 translocation Effects 0.000 description 7
- 230000035899 viability Effects 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 6
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 6
- 108010042407 Endonucleases Proteins 0.000 description 6
- 102000004533 Endonucleases Human genes 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 5
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000005520 cutting process Methods 0.000 description 5
- 101150096852 dck gene Proteins 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 4
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 4
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 4
- 230000001461 cytolytic effect Effects 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 201000005787 hematologic cancer Diseases 0.000 description 4
- 102000052088 human IL3RA Human genes 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 231100001231 less toxic Toxicity 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 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 4
- 230000004083 survival effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
- 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 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 description 3
- 108700042076 T-Cell Receptor alpha Genes Proteins 0.000 description 3
- 108700042077 T-Cell Receptor beta Genes Proteins 0.000 description 3
- 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 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 230000000735 allogeneic effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 229930182912 cyclosporin Natural products 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 229940125721 immunosuppressive agent Drugs 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 210000004896 polypeptide structure Anatomy 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 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 3
- 238000011426 transformation method Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 206010073478 Anaplastic large-cell lymphoma 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
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 208000036566 Erythroleukaemia Diseases 0.000 description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000917383 Homo sapiens Deoxycytidine kinase Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 102000018883 Interleukin-3 Receptor alpha Subunit Human genes 0.000 description 2
- 108010052781 Interleukin-3 Receptor alpha Subunit Proteins 0.000 description 2
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 description 2
- 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108010047620 Phytohemagglutinins Proteins 0.000 description 2
- 241000709664 Picornaviridae Species 0.000 description 2
- 208000032411 Refractory with Excess of Blasts Anemia Diseases 0.000 description 2
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 2
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- 238000010317 ablation therapy Methods 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 208000021841 acute erythroid leukemia Diseases 0.000 description 2
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 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 2
- 230000004075 alteration Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000002559 cytogenic effect Effects 0.000 description 2
- 238000002784 cytotoxicity assay Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 210000004700 fetal blood Anatomy 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 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
- 230000001976 improved effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000001802 infusion Methods 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
- 238000001990 intravenous administration Methods 0.000 description 2
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 2
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 230000001885 phytohemagglutinin Effects 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108010082091 pre-T cell receptor alpha Proteins 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 229960002930 sirolimus Drugs 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
- 241000894007 species Species 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
- 230000001173 tumoral effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 108010082808 4-1BB Ligand Proteins 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 208000033775 Basophilic Acute Leukemia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 102100025221 CD70 antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 1
- 241000251730 Chondrichthyes Species 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
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 206010050685 Cytokine storm Diseases 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 108090000331 Firefly luciferases 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
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 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
- 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
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 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
- 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
- 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 108020003285 Isocitrate lyase Proteins 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 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 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 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
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 102000018170 Lymphotoxin beta Receptor Human genes 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
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 241000124008 Mammalia Species 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
- 229930191564 Monensin Natural products 0.000 description 1
- 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 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100226902 Mus musculus Fcrlb gene Proteins 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 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
- 229930193140 Neomycin Natural products 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 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
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038270 Refractory anaemia with an excess of blasts Diseases 0.000 description 1
- 208000033501 Refractory anemia with excess blasts Diseases 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 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
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102000000160 Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Human genes 0.000 description 1
- 108010080432 Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Proteins 0.000 description 1
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 1
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
- 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 description 1
- 206010045170 Tumour lysis syndrome Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 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
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action 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
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 238000010322 bone marrow transplantation Methods 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
- 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
- 229940112129 campath Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
- 208000012191 childhood neoplasm Diseases 0.000 description 1
- 229960000724 cidofovir Drugs 0.000 description 1
- 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 1
- 229960000928 clofarabine Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 206010052015 cytokine release syndrome Diseases 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000002710 external beam radiation therapy Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 230000037406 food intake Effects 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
- 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
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000002513 implantation Methods 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
- 230000006698 induction Effects 0.000 description 1
- 238000011419 induction treatment Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960000485 methotrexate Drugs 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
- 238000000520 microinjection Methods 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 229960005358 monensin Drugs 0.000 description 1
- 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 1
- 239000000178 monomer Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- 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 1
- 208000016586 myelodysplastic syndrome with excess blasts Diseases 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 108010058237 plasma protein fraction Proteins 0.000 description 1
- 229940002993 plasmanate Drugs 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 229960003452 romidepsin Drugs 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 229940054269 sodium pyruvate Drugs 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
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000003014 totipotent stem cell Anatomy 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000005829 trimerization reaction Methods 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
- 208000010380 tumor lysis syndrome Diseases 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—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
-
- 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
- A61K35/26—Lymph; Lymph nodes; Thymus; Spleen; Splenocytes; Thymocytes
-
- 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
- A61K40/4217—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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- 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
- A61K2239/27—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by targeting or presenting multiple antigens
- A61K2239/28—Expressing multiple CARs, TCRs or antigens
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA201470361 | 2014-06-17 | ||
| DKPA201470361 | 2014-06-17 | ||
| PCT/EP2015/063656 WO2015193406A1 (en) | 2014-06-17 | 2015-06-17 | Cd123 specific multi-chain chimeric antigen receptor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2949325A1 true CA2949325A1 (en) | 2015-12-23 |
Family
ID=51062604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2949325A Abandoned CA2949325A1 (en) | 2014-06-17 | 2015-06-17 | Cd123 specific multi-chain chimeric antigen receptor |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20180134795A1 (enExample) |
| EP (1) | EP3158064A1 (enExample) |
| JP (1) | JP2017519502A (enExample) |
| AU (1) | AU2015276131A1 (enExample) |
| CA (1) | CA2949325A1 (enExample) |
| WO (1) | WO2015193406A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3119807T (pt) | 2014-03-19 | 2019-09-04 | Cellectis | Recetores de antigénios quiméricos específicos de cd123 para imunoterapêutica do cancro |
| EP3270936A4 (en) | 2015-03-17 | 2018-08-08 | Chimera Bioengineering Inc. | Smart car devices, de car polypeptides, side cars and uses thereof |
| US11052111B2 (en) | 2015-12-08 | 2021-07-06 | Chimera Bioengineering, Inc. | Smart CAR devices and DE CAR polypeptides for treating disease and methods for enhancing immune responses |
| EP3458077A4 (en) | 2016-05-17 | 2020-04-01 | Chimera Bioengineering Inc. | METHODS OF MANUFACTURING NEW AREAS OF ANTIGEN BINDING |
| MA45498A (fr) * | 2016-06-16 | 2019-04-24 | Memorial Sloan Kettering Cancer Center | Cellules treg génétiquement modifiées |
| CN107793481A (zh) * | 2016-08-31 | 2018-03-13 | 南京传奇生物科技有限公司 | 一种靶向人cd123的嵌合受体配体及其应用 |
| CN112481217A (zh) | 2016-09-01 | 2021-03-12 | 嵌合体生物工程公司 | Gold优化的car t-细胞 |
| AU2017338846B2 (en) * | 2016-10-04 | 2020-09-24 | Precision Biosciences, Inc. | Co-stimulatory domains for use in genetically-modified cells |
| WO2019154313A1 (zh) | 2018-02-11 | 2019-08-15 | 江苏恒瑞医药股份有限公司 | 一种分离的嵌合抗原受体以及包含其的修饰t细胞及用途 |
| WO2019160815A1 (en) | 2018-02-13 | 2019-08-22 | Chimera Bioengineering, Inc. | Coordinating gene expression using rna destabilizing elements |
| US20220403001A1 (en) | 2018-06-12 | 2022-12-22 | Obsidian Therapeutics, Inc. | Pde5 derived regulatory constructs and methods of use in immunotherapy |
| EP3870600A1 (en) | 2018-10-24 | 2021-09-01 | Obsidian Therapeutics, Inc. | Er tunable protein regulation |
| JP2022546282A (ja) | 2019-08-18 | 2022-11-04 | キメラ・バイオエンジニアリング，インコーポレーテッド | Ｇｏｌｄ制御導入遺伝子による併用療法 |
| WO2021046451A1 (en) | 2019-09-06 | 2021-03-11 | Obsidian Therapeutics, Inc. | Compositions and methods for dhfr tunable protein regulation |
| EP4168438A4 (en) * | 2020-06-22 | 2024-07-10 | Ramot at Tel-Aviv University Ltd. | Multi subunit protein modules, cells expressing same and uses thereof |
| JP7623497B2 (ja) | 2020-12-31 | 2025-01-28 | サノフイ | ＮＫｐ４６およびＣＤ１２３に結合する多機能性ナチュラルキラー（ＮＫ）細胞エンゲージャ |
| WO2023000036A1 (en) * | 2021-07-22 | 2023-01-26 | The Westmead Institute for Medical Research | Chimeric antigen receptor useful in treating cancer |
| WO2023137069A2 (en) * | 2022-01-12 | 2023-07-20 | St. Jude Children's Research Hospital, Inc. | Bispecific chimeric antigen receptors targeting grp78 and cd123 or grp78 and b7h3 |
| IL317227A (en) | 2022-05-27 | 2025-01-01 | Sanofi Sa | Combined natural killer (NK) cells bind to NKP46 and BCMA variants with FC engineering |
| WO2024094004A1 (zh) * | 2022-11-03 | 2024-05-10 | 重庆精准生物技术有限公司 | 靶向cd123的全人源抗体及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8163279B2 (en) * | 2007-04-13 | 2012-04-24 | Stemline Therapeutics, Inc. | IL3Rα antibody conjugates and uses thereof |
| CN102459342B (zh) * | 2009-04-27 | 2015-01-07 | 协和发酵麒麟株式会社 | 用于治疗血液肿瘤的抗il-3ra抗体 |
| EP2332994A1 (en) * | 2009-12-09 | 2011-06-15 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Trispecific therapeutics against acute myeloid leukaemia |
| PH12013501201A1 (en) * | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| HUE059815T2 (hu) * | 2012-05-18 | 2022-12-28 | Aptevo Res & Development Llc | Bispecifikus SCFV immunofuziós (BIF) kötõdés a CD123-hoz és a CD3-hoz |
| RU2663725C2 (ru) * | 2012-09-04 | 2018-08-08 | Селлектис | Многоцепочечный химерный антигенный рецептор и его применения |
-
2015
- 2015-06-17 AU AU2015276131A patent/AU2015276131A1/en not_active Abandoned
- 2015-06-17 WO PCT/EP2015/063656 patent/WO2015193406A1/en not_active Ceased
- 2015-06-17 CA CA2949325A patent/CA2949325A1/en not_active Abandoned
- 2015-06-17 EP EP15730754.7A patent/EP3158064A1/en not_active Withdrawn
- 2015-06-17 JP JP2016573854A patent/JP2017519502A/ja active Pending
- 2015-06-17 US US15/314,337 patent/US20180134795A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20180134795A1 (en) | 2018-05-17 |
| AU2015276131A1 (en) | 2016-11-17 |
| WO2015193406A1 (en) | 2015-12-23 |
| EP3158064A1 (en) | 2017-04-26 |
| JP2017519502A (ja) | 2017-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10544201B2 (en) | ROR1 specific multi-chain chimeric antigen receptor | |
| US20180134795A1 (en) | Cd123 specific multi-chain chimeric antigen receptor | |
| AU2015254595B2 (en) | CS1 specific multi-chain chimeric antigen receptor | |
| US20180002427A1 (en) | Cll1-specific multi-chain chimeric antigen receptor | |
| AU2015239069B2 (en) | CD33 specific Chimeric Antigen Receptors for cancer immunotherapy | |
| EP3341410B1 (en) | Chimeric antigen receptors with integrated controllable functions | |
| KR102726269B1 (ko) | 범용 항-cd22 키메라 항원 수용체 조작된 면역 세포 | |
| AU2015206040A1 (en) | Chimeric antigen receptor using antigen recognition domains derived from cartilaginous fish | |
| AU2015295348B2 (en) | ROR1 specific multi-chain chimeric antigen receptor | |
| AU2015295348A1 (en) | ROR1 specific multi-chain chimeric antigen receptor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20200831 |