CA3022611A1 - Genetically engineered cells and methods of making the same - Google Patents
Genetically engineered cells and methods of making the same Download PDFInfo
- Publication number
- CA3022611A1 CA3022611A1 CA3022611A CA3022611A CA3022611A1 CA 3022611 A1 CA3022611 A1 CA 3022611A1 CA 3022611 A CA3022611 A CA 3022611A CA 3022611 A CA3022611 A CA 3022611A CA 3022611 A1 CA3022611 A1 CA 3022611A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- domain
- cells
- composition
- grna molecule
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 290
- 239000000203 mixture Substances 0.000 claims abstract description 237
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 216
- 230000014509 gene expression Effects 0.000 claims abstract description 67
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 51
- 210000004027 cell Anatomy 0.000 claims description 511
- 108020005004 Guide RNA Proteins 0.000 claims description 440
- 108091033409 CRISPR Proteins 0.000 claims description 255
- 230000008685 targeting Effects 0.000 claims description 238
- 102000005962 receptors Human genes 0.000 claims description 217
- 108020003175 receptors Proteins 0.000 claims description 217
- 102000036639 antigens Human genes 0.000 claims description 155
- 108091007433 antigens Proteins 0.000 claims description 155
- 239000000427 antigen Substances 0.000 claims description 154
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 123
- 101100519206 Homo sapiens PDCD1 gene Proteins 0.000 claims description 123
- 101150087384 PDCD1 gene Proteins 0.000 claims description 123
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 123
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 116
- 229920001184 polypeptide Polymers 0.000 claims description 113
- 230000002068 genetic effect Effects 0.000 claims description 109
- 239000003795 chemical substances by application Substances 0.000 claims description 90
- 210000002865 immune cell Anatomy 0.000 claims description 84
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 82
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 82
- 206010028980 Neoplasm Diseases 0.000 claims description 71
- 239000002773 nucleotide Substances 0.000 claims description 70
- 125000003729 nucleotide group Chemical group 0.000 claims description 70
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 66
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 63
- 238000011534 incubation Methods 0.000 claims description 54
- -1 VEGF-R2 Proteins 0.000 claims description 53
- 230000027455 binding Effects 0.000 claims description 53
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 47
- 230000011664 signaling Effects 0.000 claims description 46
- 102000039446 nucleic acids Human genes 0.000 claims description 44
- 108020004707 nucleic acids Proteins 0.000 claims description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
- 108020004414 DNA Proteins 0.000 claims description 37
- 102000004127 Cytokines Human genes 0.000 claims description 36
- 108090000695 Cytokines Proteins 0.000 claims description 36
- 230000004068 intracellular signaling Effects 0.000 claims description 36
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims description 35
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims description 35
- 230000000139 costimulatory effect Effects 0.000 claims description 34
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 33
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 33
- 102000006306 Antigen Receptors Human genes 0.000 claims description 31
- 108010083359 Antigen Receptors Proteins 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 31
- 201000011510 cancer Diseases 0.000 claims description 30
- 108090000623 proteins and genes Proteins 0.000 claims description 30
- 210000004369 blood Anatomy 0.000 claims description 29
- 239000008280 blood Substances 0.000 claims description 29
- 238000004520 electroporation Methods 0.000 claims description 29
- 230000001939 inductive effect Effects 0.000 claims description 29
- 230000000295 complement effect Effects 0.000 claims description 28
- 230000035772 mutation Effects 0.000 claims description 27
- 239000000523 sample Substances 0.000 claims description 25
- 230000003213 activating effect Effects 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 24
- 230000026683 transduction Effects 0.000 claims description 24
- 238000010361 transduction Methods 0.000 claims description 24
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 23
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 23
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 22
- 208000008383 Wilms tumor Diseases 0.000 claims description 22
- 208000026448 Wilms tumor 1 Diseases 0.000 claims description 22
- 102100022748 Wilms tumor protein Human genes 0.000 claims description 22
- 101710127857 Wilms tumor protein Proteins 0.000 claims description 22
- 238000003776 cleavage reaction Methods 0.000 claims description 22
- 230000007017 scission Effects 0.000 claims description 22
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 21
- 102000003735 Mesothelin Human genes 0.000 claims description 21
- 108090000015 Mesothelin Proteins 0.000 claims description 21
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 21
- 230000004936 stimulating effect Effects 0.000 claims description 21
- 239000012636 effector Substances 0.000 claims description 20
- 238000000338 in vitro Methods 0.000 claims description 20
- 239000003446 ligand Substances 0.000 claims description 20
- 239000012634 fragment Substances 0.000 claims description 19
- 230000006780 non-homologous end joining Effects 0.000 claims description 19
- 238000011144 upstream manufacturing Methods 0.000 claims description 19
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 18
- 230000003834 intracellular effect Effects 0.000 claims description 18
- 239000001226 triphosphate Substances 0.000 claims description 18
- 235000011178 triphosphate Nutrition 0.000 claims description 18
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 18
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 claims description 17
- 230000002688 persistence Effects 0.000 claims description 17
- 239000013598 vector Substances 0.000 claims description 17
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 16
- 101150029707 ERBB2 gene Proteins 0.000 claims description 16
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 16
- 101001018097 Homo sapiens L-selectin Proteins 0.000 claims description 16
- 108010002350 Interleukin-2 Proteins 0.000 claims description 16
- 102000000588 Interleukin-2 Human genes 0.000 claims description 16
- 102100033467 L-selectin Human genes 0.000 claims description 16
- 239000002269 analeptic agent Substances 0.000 claims description 16
- 230000035755 proliferation Effects 0.000 claims description 16
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims description 14
- 102100024964 Neural cell adhesion molecule L1 Human genes 0.000 claims description 14
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 13
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 claims description 13
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 claims description 13
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 13
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 13
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 claims description 13
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 claims description 13
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 13
- 102000003812 Interleukin-15 Human genes 0.000 claims description 13
- 108090000172 Interleukin-15 Proteins 0.000 claims description 13
- 102100034256 Mucin-1 Human genes 0.000 claims description 13
- 102100036735 Prostate stem cell antigen Human genes 0.000 claims description 13
- 231100000135 cytotoxicity Toxicity 0.000 claims description 13
- 230000003013 cytotoxicity Effects 0.000 claims description 13
- 238000012217 deletion Methods 0.000 claims description 13
- 230000037430 deletion Effects 0.000 claims description 13
- 230000001605 fetal effect Effects 0.000 claims description 13
- 210000000265 leukocyte Anatomy 0.000 claims description 13
- 230000028327 secretion Effects 0.000 claims description 13
- 210000001519 tissue Anatomy 0.000 claims description 13
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 12
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 12
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 12
- 102100032912 CD44 antigen Human genes 0.000 claims description 12
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 12
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims description 12
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 12
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 claims description 12
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 claims description 12
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 12
- 101800001271 Surface protein Proteins 0.000 claims description 12
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 11
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 11
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 claims description 11
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 claims description 11
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 claims description 11
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 11
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 claims description 11
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 11
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 claims description 11
- 108010002586 Interleukin-7 Proteins 0.000 claims description 11
- 102000000704 Interleukin-7 Human genes 0.000 claims description 11
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 claims description 11
- 102100022430 Melanocyte protein PMEL Human genes 0.000 claims description 11
- 102100023123 Mucin-16 Human genes 0.000 claims description 11
- 102100038081 Signal transducer CD24 Human genes 0.000 claims description 11
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 11
- 239000012472 biological sample Substances 0.000 claims description 11
- 102000015694 estrogen receptors Human genes 0.000 claims description 11
- 108010038795 estrogen receptors Proteins 0.000 claims description 11
- 238000000684 flow cytometry Methods 0.000 claims description 11
- 208000002672 hepatitis B Diseases 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 102000003998 progesterone receptors Human genes 0.000 claims description 11
- 108090000468 progesterone receptors Proteins 0.000 claims description 11
- 230000004083 survival effect Effects 0.000 claims description 11
- 239000013603 viral vector Substances 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 10
- 208000035473 Communicable disease Diseases 0.000 claims description 10
- 108050006400 Cyclin Proteins 0.000 claims description 10
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 10
- 230000003432 anti-folate effect Effects 0.000 claims description 10
- 229940127074 antifolate Drugs 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 239000004052 folic acid antagonist Substances 0.000 claims description 10
- 101001051490 Homo sapiens Neural cell adhesion molecule L1 Proteins 0.000 claims description 9
- 238000000099 in vitro assay Methods 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- 238000013518 transcription Methods 0.000 claims description 9
- 230000035897 transcription Effects 0.000 claims description 9
- 230000009261 transgenic effect Effects 0.000 claims description 9
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 claims description 9
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 claims description 8
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 claims description 8
- 239000000872 buffer Substances 0.000 claims description 8
- 210000000822 natural killer cell Anatomy 0.000 claims description 8
- 210000000130 stem cell Anatomy 0.000 claims description 8
- 102100027207 CD27 antigen Human genes 0.000 claims description 7
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 7
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 7
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 7
- 108010065805 Interleukin-12 Proteins 0.000 claims description 7
- 102000013462 Interleukin-12 Human genes 0.000 claims description 7
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 7
- 210000005260 human cell Anatomy 0.000 claims description 7
- 229940117681 interleukin-12 Drugs 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 108060003951 Immunoglobulin Proteins 0.000 claims description 6
- 206010025323 Lymphomas Diseases 0.000 claims description 6
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 6
- 102000018358 immunoglobulin Human genes 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 210000004698 lymphocyte Anatomy 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 230000001177 retroviral effect Effects 0.000 claims description 6
- 108700028369 Alleles Proteins 0.000 claims description 5
- 238000003780 insertion Methods 0.000 claims description 5
- 230000037431 insertion Effects 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 claims description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000000172 Medulloblastoma Diseases 0.000 claims description 4
- 206010027406 Mesothelioma Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 claims description 4
- 230000005782 double-strand break Effects 0.000 claims description 4
- 230000001747 exhibiting effect Effects 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 230000003248 secreting effect Effects 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 3
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 claims description 3
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 3
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 claims description 3
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 claims description 3
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 3
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 230000008901 benefit Effects 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 238000002513 implantation Methods 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000000284 resting effect Effects 0.000 claims description 2
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 8
- 102000008160 Cyclin A1 Human genes 0.000 claims 8
- 108010060267 Cyclin A1 Proteins 0.000 claims 8
- 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 claims 6
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 claims 6
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 claims 6
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims 6
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims 6
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims 6
- 102000007066 Prostate-Specific Antigen Human genes 0.000 claims 6
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 6
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 6
- 238000012737 microarray-based gene expression Methods 0.000 claims 6
- 238000012243 multiplex automated genomic engineering Methods 0.000 claims 6
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 6
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 6
- 101150047061 tag-72 gene Proteins 0.000 claims 6
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 claims 5
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 claims 5
- 101710112634 Interleukin-13 receptor subunit alpha-2 Proteins 0.000 claims 5
- 108010012255 Neural Cell Adhesion Molecule L1 Proteins 0.000 claims 5
- 102000016736 Cyclin Human genes 0.000 claims 4
- 101001051488 Takifugu rubripes Neural cell adhesion molecule L1 Proteins 0.000 claims 3
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims 2
- 208000003950 B-cell lymphoma Diseases 0.000 claims 2
- 206010005949 Bone cancer Diseases 0.000 claims 2
- 208000018084 Bone neoplasm Diseases 0.000 claims 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims 2
- 201000009030 Carcinoma Diseases 0.000 claims 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 2
- 208000017604 Hodgkin disease Diseases 0.000 claims 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 2
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims 2
- 208000019065 cervical carcinoma Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 201000003444 follicular lymphoma Diseases 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 201000007270 liver cancer Diseases 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 230000036210 malignancy Effects 0.000 claims 2
- 201000008968 osteosarcoma Diseases 0.000 claims 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims 2
- 201000000849 skin cancer Diseases 0.000 claims 2
- 206010042863 synovial sarcoma Diseases 0.000 claims 2
- 102100025390 Integrin beta-2 Human genes 0.000 claims 1
- 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract description 8
- 238000002619 cancer immunotherapy Methods 0.000 abstract description 3
- 238000012546 transfer Methods 0.000 abstract description 3
- 210000000173 T-lymphoid precursor cell Anatomy 0.000 abstract description 2
- 101100113998 Mus musculus Cnbd2 gene Proteins 0.000 abstract 1
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 87
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 80
- 108091008874 T cell receptors Proteins 0.000 description 75
- 229940024606 amino acid Drugs 0.000 description 52
- 235000001014 amino acid Nutrition 0.000 description 52
- 150000001413 amino acids Chemical class 0.000 description 50
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 42
- 102000004389 Ribonucleoproteins Human genes 0.000 description 34
- 108010081734 Ribonucleoproteins Proteins 0.000 description 34
- 125000006850 spacer group Chemical group 0.000 description 28
- 239000003550 marker Substances 0.000 description 24
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 21
- 238000000926 separation method Methods 0.000 description 17
- 101710153660 Nuclear receptor corepressor 2 Proteins 0.000 description 14
- 230000001086 cytosolic effect Effects 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 125000005647 linker group Chemical group 0.000 description 14
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 14
- 230000004913 activation Effects 0.000 description 12
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 238000011467 adoptive cell therapy Methods 0.000 description 10
- 210000003071 memory t lymphocyte Anatomy 0.000 description 10
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 description 9
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000012384 transportation and delivery Methods 0.000 description 9
- 108050008953 Melanoma-associated antigen Proteins 0.000 description 8
- 102100030569 Nuclear receptor corepressor 2 Human genes 0.000 description 8
- 102100026497 Zinc finger protein 654 Human genes 0.000 description 8
- 108700012439 CA9 Proteins 0.000 description 7
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 7
- 108010008707 Mucin-1 Proteins 0.000 description 7
- 101710120463 Prostate stem cell antigen Proteins 0.000 description 7
- 101001039269 Rattus norvegicus Glycine N-methyltransferase Proteins 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000010353 genetic engineering Methods 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 102100031507 Fc receptor-like protein 5 Human genes 0.000 description 6
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 6
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 6
- 108700010039 chimeric receptor Proteins 0.000 description 6
- 108091008034 costimulatory receptors Proteins 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000000717 retained effect Effects 0.000 description 6
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 5
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 101000846908 Homo sapiens Fc receptor-like protein 5 Proteins 0.000 description 4
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- 101001095088 Homo sapiens Melanoma antigen preferentially expressed in tumors Proteins 0.000 description 4
- 101000662902 Homo sapiens T cell receptor beta constant 2 Proteins 0.000 description 4
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 4
- 102000007482 Interleukin-13 Receptor alpha2 Subunit Human genes 0.000 description 4
- 108010085418 Interleukin-13 Receptor alpha2 Subunit Proteins 0.000 description 4
- 102100037020 Melanoma antigen preferentially expressed in tumors Human genes 0.000 description 4
- 241000588650 Neisseria meningitidis Species 0.000 description 4
- 102100038358 Prostate-specific antigen Human genes 0.000 description 4
- 241000194020 Streptococcus thermophilus Species 0.000 description 4
- 102100033579 Trophoblast glycoprotein Human genes 0.000 description 4
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 238000002659 cell therapy Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 210000002443 helper t lymphocyte Anatomy 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 102100036841 C-C motif chemokine 1 Human genes 0.000 description 3
- 108010058905 CD44v6 antigen Proteins 0.000 description 3
- 102000000844 Cell Surface Receptors Human genes 0.000 description 3
- 108010001857 Cell Surface Receptors Proteins 0.000 description 3
- 108010009685 Cholinergic Receptors Proteins 0.000 description 3
- 101000713104 Homo sapiens C-C motif chemokine 1 Proteins 0.000 description 3
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 description 3
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 3
- 101000801433 Homo sapiens Trophoblast glycoprotein Proteins 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 3
- 102100023616 Neural cell adhesion molecule L1-like protein Human genes 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 102100037298 T cell receptor beta constant 2 Human genes 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 3
- 102000034337 acetylcholine receptors Human genes 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 238000002617 apheresis Methods 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 239000002458 cell surface marker Substances 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 102000006495 integrins Human genes 0.000 description 3
- 108010044426 integrins Proteins 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 210000004986 primary T-cell Anatomy 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 3
- SSOORFWOBGFTHL-OTEJMHTDSA-N (4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SSOORFWOBGFTHL-OTEJMHTDSA-N 0.000 description 2
- 108090000672 Annexin A5 Proteins 0.000 description 2
- 102000004121 Annexin A5 Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 2
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 2
- 108010060273 Cyclin A2 Proteins 0.000 description 2
- 102100025191 Cyclin-A2 Human genes 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 101150032879 Fcrl5 gene Proteins 0.000 description 2
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102100037931 Harmonin Human genes 0.000 description 2
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 2
- 101000805947 Homo sapiens Harmonin Proteins 0.000 description 2
- 101001057156 Homo sapiens Melanoma-associated antigen C2 Proteins 0.000 description 2
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 102100022339 Integrin alpha-L Human genes 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 108010010995 MART-1 Antigen Proteins 0.000 description 2
- 102100027252 Melanoma-associated antigen C2 Human genes 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 2
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 2
- 108010002687 Survivin Proteins 0.000 description 2
- 102100036234 Synaptonemal complex protein 1 Human genes 0.000 description 2
- 102100035721 Syndecan-1 Human genes 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 101710171981 Volume-regulated anion channel subunit LRRC8A Proteins 0.000 description 2
- 102100040985 Volume-regulated anion channel subunit LRRC8A Human genes 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000003162 effector t lymphocyte Anatomy 0.000 description 2
- 210000004700 fetal blood Anatomy 0.000 description 2
- 229940014144 folate Drugs 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- 108091008042 inhibitory receptors Proteins 0.000 description 2
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 230000005291 magnetic effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000000066 myeloid cell Anatomy 0.000 description 2
- PUPNJSIFIXXJCH-UHFFFAOYSA-N n-(4-hydroxyphenyl)-2-(1,1,3-trioxo-1,2-benzothiazol-2-yl)acetamide Chemical compound C1=CC(O)=CC=C1NC(=O)CN1S(=O)(=O)C2=CC=CC=C2C1=O PUPNJSIFIXXJCH-UHFFFAOYSA-N 0.000 description 2
- 210000000581 natural killer T-cell Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000009437 off-target effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 102100023003 Ankyrin repeat domain-containing protein 30A Human genes 0.000 description 1
- 102100033680 Bombesin receptor-activated protein C6orf89 Human genes 0.000 description 1
- 102100037904 CD9 antigen Human genes 0.000 description 1
- 108010083123 CDX2 Transcription Factor Proteins 0.000 description 1
- 102000006277 CDX2 Transcription Factor Human genes 0.000 description 1
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102100039510 Cancer/testis antigen 2 Human genes 0.000 description 1
- 101100495352 Candida albicans CDR4 gene Proteins 0.000 description 1
- 102100027668 Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 Human genes 0.000 description 1
- 101710134395 Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102100032952 Condensin complex subunit 3 Human genes 0.000 description 1
- 102100025571 Cutaneous T-cell lymphoma-associated antigen 1 Human genes 0.000 description 1
- 102100033587 DNA topoisomerase 2-alpha Human genes 0.000 description 1
- 102100033589 DNA topoisomerase 2-beta Human genes 0.000 description 1
- 102100031695 DnaJ homolog subfamily C member 2 Human genes 0.000 description 1
- 102100034185 E3 ubiquitin-protein ligase RLIM Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 102100031812 Fibulin-1 Human genes 0.000 description 1
- 101710170731 Fibulin-1 Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 102000010451 Folate receptor alpha Human genes 0.000 description 1
- 108050001931 Folate receptor alpha Proteins 0.000 description 1
- 102100020714 Fragile X mental retardation 1 neighbor protein Human genes 0.000 description 1
- 102100031351 Galectin-9 Human genes 0.000 description 1
- 101710121810 Galectin-9 Proteins 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 102100022650 Homeobox protein Hox-A7 Human genes 0.000 description 1
- 102100025056 Homeobox protein Hox-B6 Human genes 0.000 description 1
- 101000757191 Homo sapiens Ankyrin repeat domain-containing protein 30A Proteins 0.000 description 1
- 101000984746 Homo sapiens BRCA1-associated protein Proteins 0.000 description 1
- 101000944524 Homo sapiens Bombesin receptor-activated protein C6orf89 Proteins 0.000 description 1
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 1
- 101000889345 Homo sapiens Cancer/testis antigen 2 Proteins 0.000 description 1
- 101000942622 Homo sapiens Condensin complex subunit 3 Proteins 0.000 description 1
- 101000856239 Homo sapiens Cutaneous T-cell lymphoma-associated antigen 1 Proteins 0.000 description 1
- 101000845887 Homo sapiens DnaJ homolog subfamily C member 2 Proteins 0.000 description 1
- 101000711924 Homo sapiens E3 ubiquitin-protein ligase RLIM Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000932499 Homo sapiens Fragile X mental retardation 1 neighbor protein Proteins 0.000 description 1
- 101000986084 Homo sapiens HLA class I histocompatibility antigen, C alpha chain Proteins 0.000 description 1
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 101001045116 Homo sapiens Homeobox protein Hox-A7 Proteins 0.000 description 1
- 101001077542 Homo sapiens Homeobox protein Hox-B6 Proteins 0.000 description 1
- 101000911772 Homo sapiens Hsc70-interacting protein Proteins 0.000 description 1
- 101100452137 Homo sapiens IGF2BP3 gene Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001055145 Homo sapiens Interleukin-2 receptor subunit beta Proteins 0.000 description 1
- 101001008951 Homo sapiens Kinesin-like protein KIF15 Proteins 0.000 description 1
- 101001054842 Homo sapiens Leucine zipper protein 4 Proteins 0.000 description 1
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 1
- 101000576802 Homo sapiens Mesothelin Proteins 0.000 description 1
- 101000874141 Homo sapiens Probable ATP-dependent RNA helicase DDX43 Proteins 0.000 description 1
- 101000880770 Homo sapiens Protein SSX2 Proteins 0.000 description 1
- 101000880771 Homo sapiens Protein SSX3 Proteins 0.000 description 1
- 101000880774 Homo sapiens Protein SSX4 Proteins 0.000 description 1
- 101000880775 Homo sapiens Protein SSX5 Proteins 0.000 description 1
- 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
- 101000743264 Homo sapiens RNA-binding protein 6 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000756066 Homo sapiens Serine/threonine-protein kinase RIO1 Proteins 0.000 description 1
- 101000628562 Homo sapiens Serine/threonine-protein kinase STK11 Proteins 0.000 description 1
- 101000632529 Homo sapiens Shugoshin 1 Proteins 0.000 description 1
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 description 1
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000784541 Homo sapiens Zinc finger and SCAN domain-containing protein 21 Proteins 0.000 description 1
- 101000785712 Homo sapiens Zinc finger protein 282 Proteins 0.000 description 1
- 101000856240 Homo sapiens cTAGE family member 2 Proteins 0.000 description 1
- 102100027037 Hsc70-interacting protein Human genes 0.000 description 1
- 102100027735 Hyaluronan mediated motility receptor Human genes 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102100037920 Insulin-like growth factor 2 mRNA-binding protein 3 Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 1
- 102100027630 Kinesin-like protein KIF15 Human genes 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 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 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100026910 Leucine zipper protein 4 Human genes 0.000 description 1
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 1
- 241000186805 Listeria innocua Species 0.000 description 1
- 102100033247 Lysine-specific demethylase 5B Human genes 0.000 description 1
- 101710105712 Lysine-specific demethylase 5B Proteins 0.000 description 1
- 102000016200 MART-1 Antigen Human genes 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102100025096 Mesothelin Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 1
- 241000701029 Murid betaherpesvirus 1 Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100508818 Mus musculus Inpp5k gene Proteins 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 102100026949 Opioid growth factor receptor Human genes 0.000 description 1
- 101710130302 Opioid growth factor receptor Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102100035724 Probable ATP-dependent RNA helicase DDX43 Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102100037686 Protein SSX2 Human genes 0.000 description 1
- 102100037726 Protein SSX3 Human genes 0.000 description 1
- 102100037727 Protein SSX4 Human genes 0.000 description 1
- 102100037723 Protein SSX5 Human genes 0.000 description 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
- 102100038150 RNA-binding protein 6 Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100366438 Rattus norvegicus Sphkap gene Proteins 0.000 description 1
- 108010006700 Receptor Tyrosine Kinase-like Orphan Receptors Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100029627 Ribosomal RNA processing protein 1 homolog A Human genes 0.000 description 1
- 101710166144 Ribosomal RNA processing protein 1 homolog A Proteins 0.000 description 1
- 102100022261 Serine/threonine-protein kinase RIO1 Human genes 0.000 description 1
- 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 description 1
- 102100028402 Shugoshin 1 Human genes 0.000 description 1
- 241000194019 Streptococcus mutans Species 0.000 description 1
- 101710143177 Synaptonemal complex protein 1 Proteins 0.000 description 1
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 description 1
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 101150002618 TCRP gene Proteins 0.000 description 1
- 101710190034 Trophoblast glycoprotein Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 1
- 102100039094 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 102100020917 Zinc finger and SCAN domain-containing protein 21 Human genes 0.000 description 1
- 102100026417 Zinc finger protein 282 Human genes 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- MXKCYTKUIDTFLY-ZNNSSXPHSA-N alpha-L-Fucp-(1->2)-beta-D-Galp-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc-(1->3)-D-Galp Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](NC(C)=O)[C@H](O[C@H]3[C@H]([C@@H](CO)OC(O)[C@@H]3O)O)O[C@@H]2CO)O[C@H]2[C@H]([C@H](O)[C@H](O)[C@H](C)O2)O)O[C@H](CO)[C@H](O)[C@@H]1O MXKCYTKUIDTFLY-ZNNSSXPHSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- CXQCLLQQYTUUKJ-ALWAHNIESA-N beta-D-GalpNAc-(1->4)-[alpha-Neup5Ac-(2->8)-alpha-Neup5Ac-(2->3)]-beta-D-Galp-(1->4)-beta-D-Glcp-(1<->1')-Cer(d18:1/18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@@H](CO)O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 CXQCLLQQYTUUKJ-ALWAHNIESA-N 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000003320 cell separation method Methods 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 238000007822 cytometric assay Methods 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound 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 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000004837 gut-associated lymphoid tissue Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 108010003425 hyaluronan-mediated motility receptor Proteins 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 210000002861 immature t-cell Anatomy 0.000 description 1
- 229940126546 immune checkpoint molecule Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 108010027445 interleukin-22 receptor Proteins 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 210000004990 primary immune cell Anatomy 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 231100000617 superantigen Toxicity 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- 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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—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
- A61K40/40—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
- A61K40/421—Immunoglobulin superfamily
- A61K40/4211—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- 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
- C07K16/2878—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 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- 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
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
- A61K2239/48—Blood cells, e.g. leukemia or lymphoma
-
- 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
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
- A61K2239/55—Lung
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/317—Chemical structure of the backbone with an inverted bond, e.g. a cap structure
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/336—Modified G
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2302—Interleukin-2 (IL-2)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2307—Interleukin-7 (IL-7)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2315—Interleukin-15 (IL-15)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/51—B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/515—CD3, T-cell receptor complex
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/998—Proteins not provided for elsewhere
-
- 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
-
- 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
- C12N2523/00—Culture process characterised by temperature
-
- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662333144P | 2016-05-06 | 2016-05-06 | |
| US201662332657P | 2016-05-06 | 2016-05-06 | |
| US62/332,657 | 2016-05-06 | ||
| US62/333,144 | 2016-05-06 | ||
| PCT/US2017/031464 WO2017193107A2 (en) | 2016-05-06 | 2017-05-06 | Genetically engineered cells and methods of making the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3022611A1 true CA3022611A1 (en) | 2017-11-09 |
Family
ID=58800896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3022611A Pending CA3022611A1 (en) | 2016-05-06 | 2017-05-06 | Genetically engineered cells and methods of making the same |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20190136230A1 (enExample) |
| EP (1) | EP3452499A2 (enExample) |
| JP (2) | JP2019517788A (enExample) |
| KR (2) | KR20230038299A (enExample) |
| CN (2) | CN116850305A (enExample) |
| AU (2) | AU2017261380A1 (enExample) |
| CA (1) | CA3022611A1 (enExample) |
| IL (2) | IL262772B2 (enExample) |
| MA (1) | MA44869A (enExample) |
| MX (2) | MX2018013445A (enExample) |
| SG (1) | SG11201809710RA (enExample) |
| WO (1) | WO2017193107A2 (enExample) |
Families Citing this family (120)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| CA2935960C (en) | 2014-01-08 | 2023-01-10 | Bart Lipkens | Acoustophoresis device with dual acoustophoretic chamber |
| MX2017000646A (es) | 2014-07-15 | 2017-04-27 | Juno Therapeutics Inc | Celulas geneticamente modificadas para terapia celular adoptiva. |
| WO2016154596A1 (en) * | 2015-03-25 | 2016-09-29 | Editas Medicine, Inc. | Crispr/cas-related methods, compositions and components |
| 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 |
| DE112016002056T5 (de) | 2015-05-06 | 2018-02-08 | Snipr Technologies Limited | Verändern mikrobieller Populationen und Modifizieren von Mikrobiomen |
| MA42895A (fr) | 2015-07-15 | 2018-05-23 | Juno Therapeutics Inc | Cellules modifiées pour thérapie cellulaire adoptive |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| GB201609811D0 (en) | 2016-06-05 | 2016-07-20 | Snipr Technologies Ltd | Methods, cells, systems, arrays, RNA and kits |
| US11293021B1 (en) | 2016-06-23 | 2022-04-05 | Inscripta, Inc. | Automated cell processing methods, modules, instruments, and systems |
| GB201700621D0 (en) | 2017-01-13 | 2017-03-01 | Guest Ryan Dominic | Method,device and kit for the aseptic isolation,enrichment and stabilsation of cells from mammalian solid tissue |
| MY201573A (en) * | 2017-05-12 | 2024-03-02 | Crispr Therapeutics Ag | Materials and methods for engineering cells and uses thereof in immuno-oncology |
| US9982279B1 (en) | 2017-06-23 | 2018-05-29 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| US10011849B1 (en) | 2017-06-23 | 2018-07-03 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| KR102424850B1 (ko) | 2017-06-30 | 2022-07-22 | 인스크립타 인코포레이티드 | 자동 세포 처리 방법, 모듈, 기기 및 시스템 |
| CN109517820B (zh) | 2017-09-20 | 2021-09-24 | 北京宇繁生物科技有限公司 | 一种靶向HPK1的gRNA以及HPK1基因编辑方法 |
| WO2019070541A1 (en) | 2017-10-03 | 2019-04-11 | Juno Therapeutics, Inc. | HPV-SPECIFIC BINDING MOLECULES |
| CN111556893A (zh) * | 2017-11-06 | 2020-08-18 | 爱迪塔斯医药股份有限公司 | 免疫疗法t细胞中cblb的crispr-cas9编辑的方法、组合物和组分 |
| CN120310773A (zh) * | 2017-11-16 | 2025-07-15 | 阿斯利康(瑞典)有限公司 | 用于改善基于Cas9的敲入策略的有效性的组合物和方法 |
| KR20220066413A (ko) | 2017-12-14 | 2022-05-24 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| US10760075B2 (en) | 2018-04-30 | 2020-09-01 | Snipr Biome Aps | Treating and preventing microbial infections |
| SG11202009446TA (en) | 2018-04-05 | 2020-10-29 | Juno Therapeutics Inc | T cells expressing a recombinant receptor, related polynucleotides and methods |
| MA52656A (fr) | 2018-04-05 | 2021-02-17 | Editas Medicine Inc | Procédés de production de cellules exprimant un récepteur recombinant et compositions associées |
| RU2020135968A (ru) | 2018-04-05 | 2022-05-06 | Джуно Терапьютикс, Инк. | T-клеточные рецепторы и модифицированные клетки, экспрессирующие |
| EP3775213A1 (en) * | 2018-04-13 | 2021-02-17 | Sigma Aldrich Co. LLC | Modification of immune-related genomic loci using paired crispr nickase ribonucleoproteins |
| US10858761B2 (en) | 2018-04-24 | 2020-12-08 | Inscripta, Inc. | Nucleic acid-guided editing of exogenous polynucleotides in heterologous cells |
| US10526598B2 (en) | 2018-04-24 | 2020-01-07 | Inscripta, Inc. | Methods for identifying T-cell receptor antigens |
| JP7542441B2 (ja) | 2018-05-11 | 2024-08-30 | クリスパー セラピューティクス アクチェンゲゼルシャフト | 癌を治療するための方法及び組成物 |
| KR20210045360A (ko) | 2018-05-16 | 2021-04-26 | 신테고 코포레이션 | 가이드 rna 설계 및 사용을 위한 방법 및 시스템 |
| CN112867498A (zh) * | 2018-05-31 | 2021-05-28 | 华盛顿大学 | 使用嵌合抗原受体基因组编辑和转导t细胞以用于治疗t和b细胞恶性肿瘤的方法 |
| WO2019232370A1 (en) * | 2018-06-01 | 2019-12-05 | Mayo Foundation For Medical Education And Research | Materials and methods for treating cancer |
| AU2019292919A1 (en) | 2018-06-30 | 2021-03-11 | Inscripta, Inc. | Instruments, modules, and methods for improved detection of edited sequences in live cells |
| US11142740B2 (en) | 2018-08-14 | 2021-10-12 | Inscripta, Inc. | Detection of nuclease edited sequences in automated modules and instruments |
| US11214781B2 (en) | 2018-10-22 | 2022-01-04 | Inscripta, Inc. | Engineered enzyme |
| CN109652380B (zh) * | 2019-01-25 | 2023-04-28 | 苏州茂行生物科技有限公司 | 基于碱基编辑靶向LewisY的CAR-T细胞及其制备方法和应用 |
| CN110527695B (zh) * | 2019-03-07 | 2020-06-16 | 山东舜丰生物科技有限公司 | 一种用于基因定点突变的核酸构建物 |
| EP3947691A4 (en) | 2019-03-25 | 2022-12-14 | Inscripta, Inc. | SIMULTANEOUS MULTIPLEX GENOME EDITING IN A YEAST |
| US11001831B2 (en) | 2019-03-25 | 2021-05-11 | Inscripta, Inc. | Simultaneous multiplex genome editing in yeast |
| RU2731293C1 (ru) | 2019-04-12 | 2020-09-01 | Игорь Петрович Белецкий | Способ получения генно-модифицированных линий клеток натуральных киллеров с нокаутированным геном PD-1 и повышенной экспрессией белков семейства Фактора Некроза Опухолей для иммунотерапии онкологических заболеваний |
| BR112021021075A2 (pt) | 2019-05-01 | 2021-12-14 | Editas Medicine Inc | Células que expressam um receptor recombinante de um locus de tgfbr2 modificado, polinucleotídeos relacionados e métodos |
| KR20220016474A (ko) | 2019-05-01 | 2022-02-09 | 주노 쎄러퓨티크스 인코퍼레이티드 | 변형된 cd247 유전자 자리로부터 키메라 수용체를 발현하는 세포, 관련 폴리뉴클레오타이드 및 방법 |
| CN113939593A (zh) | 2019-06-06 | 2022-01-14 | 因思科瑞普特公司 | 用于递归的核酸指导的细胞编辑的处治 |
| AU2020314956A1 (en) * | 2019-07-17 | 2022-03-03 | Case Western Reserve University | Long lived T cells for treating HIV infection |
| EP3999651A4 (en) * | 2019-08-26 | 2023-07-26 | PACT Pharma, Inc. | METHOD OF EXECUTING GUIDE-SEQ ON PRIMARY HUMAN T-CELLS |
| AU2020342207A1 (en) * | 2019-09-04 | 2022-04-21 | Edigene (Guangzhou) Inc. | Method for evaluating gene editing therapy based on off-target assessment |
| AU2020343516A1 (en) * | 2019-09-06 | 2022-03-10 | Crispr Therapeutics Ag | Genetically engineered T cells having improved persistence in culture |
| JP7696335B2 (ja) | 2019-09-09 | 2025-06-20 | スクライブ・セラピューティクス・インコーポレイテッド | 免疫療法に使用するための組成物および方法 |
| EP4053285A4 (en) * | 2019-10-29 | 2024-06-19 | Genkore Inc | GUIDE RNA MODIFIED TO INCREASE THE EFFICIENCY OF CRISPR/CAS12F1 SYSTEM, AND ITS USE |
| CN114901808A (zh) * | 2019-11-13 | 2022-08-12 | 克里斯珀医疗股份公司 | 生产car-t细胞的方法 |
| IL292329A (en) * | 2019-11-13 | 2022-06-01 | Crispr Therapeutics Ag | Manufacturing process for making t cells expressing chimeric antigen receptors |
| WO2021102059A1 (en) | 2019-11-19 | 2021-05-27 | Inscripta, Inc. | Methods for increasing observed editing in bacteria |
| US20230009232A1 (en) * | 2019-11-20 | 2023-01-12 | Cartherics Pty. Ltd. | Method for providing immune cells with enhanced function |
| US20230008217A1 (en) * | 2019-12-17 | 2023-01-12 | Agilent Technologies, Inc. | Ligation-based gene editing using crispr nickase |
| CN114829607A (zh) | 2019-12-18 | 2022-07-29 | 因思科瑞普特公司 | 用于体内检测核酸引导的核酸酶编辑的细胞的Cascade/dCas3互补测定 |
| WO2021123832A1 (en) | 2019-12-20 | 2021-06-24 | Instil Bio (Uk) Limited | Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof |
| CN110964744A (zh) * | 2019-12-23 | 2020-04-07 | 湖南普拉特泽生物科技有限公司 | 一种能稳定表达Cas9蛋白的人骨肉瘤U-2OS工具细胞株及其制备方法与应用 |
| CN110951782A (zh) * | 2019-12-23 | 2020-04-03 | 湖南普拉特网络科技有限公司 | 一种能稳定表达Cas9蛋白的细胞株及其制备方法与应用 |
| CN115003802B (zh) * | 2020-01-02 | 2024-09-03 | 宁波茂行生物医药科技有限公司 | 一种经修饰的免疫效应细胞及其制备方法 |
| TW202140790A (zh) * | 2020-01-22 | 2021-11-01 | 愛爾蘭商佧琺藥業有限公司 | 病毒載體轉導細胞的方法 |
| WO2021154706A1 (en) | 2020-01-27 | 2021-08-05 | Inscripta, Inc. | Electroporation modules and instrumentation |
| US20210238535A1 (en) * | 2020-02-02 | 2021-08-05 | Inscripta, Inc. | Automated production of car-expressing cells |
| US20230165909A1 (en) | 2020-04-21 | 2023-06-01 | Aspen Neuroscience, Inc. | Gene editing of lrrk2 in stem cells and method of use of cells differentiated therefrom |
| WO2021216622A1 (en) | 2020-04-21 | 2021-10-28 | Aspen Neuroscience, Inc. | Gene editing of gba1 in stem cells and method of use of cells differentiated therefrom |
| US20210332388A1 (en) | 2020-04-24 | 2021-10-28 | Inscripta, Inc. | Compositions, methods, modules and instruments for automated nucleic acid-guided nuclease editing in mammalian cells |
| EP4146800A1 (en) * | 2020-05-08 | 2023-03-15 | Metagenomi, Inc. | Enzymes with ruvc domains |
| US11787841B2 (en) | 2020-05-19 | 2023-10-17 | Inscripta, Inc. | Rationally-designed mutations to the thrA gene for enhanced lysine production in E. coli |
| EP4171616A1 (en) | 2020-06-26 | 2023-05-03 | Juno Therapeutics GmbH | Engineered t cells conditionally expressing a recombinant receptor, related polynucleotides and methods |
| EP4214314A4 (en) | 2020-09-15 | 2024-10-16 | Inscripta, Inc. | Crispr editing to embed nucleic acid landing pads into genomes of live cells |
| KR20230090367A (ko) | 2020-11-04 | 2023-06-21 | 주노 쎄러퓨티크스 인코퍼레이티드 | 변형된 불변 cd3 이뮤노글로불린 슈퍼패밀리 쇄 유전자좌로부터 키메라 수용체를 발현하는 세포 및 관련 폴리뉴클레오티드 및 방법 |
| US11512297B2 (en) | 2020-11-09 | 2022-11-29 | Inscripta, Inc. | Affinity tag for recombination protein recruitment |
| WO2022132756A1 (en) * | 2020-12-14 | 2022-06-23 | Emendobio Inc. | Biallelic knockout of trac |
| US11306298B1 (en) | 2021-01-04 | 2022-04-19 | Inscripta, Inc. | Mad nucleases |
| US11332742B1 (en) | 2021-01-07 | 2022-05-17 | Inscripta, Inc. | Mad nucleases |
| WO2022170059A1 (en) | 2021-02-05 | 2022-08-11 | Christiana Care Health Services, Inc. | Methods of and compositions for reducing gene expression and/or activity |
| US11884924B2 (en) | 2021-02-16 | 2024-01-30 | Inscripta, Inc. | Dual strand nucleic acid-guided nickase editing |
| US20240108654A1 (en) | 2021-03-03 | 2024-04-04 | Juno Therapeutics, Inc. | Combination of a t cell therapy and a dgk inhibitor |
| KR20240027117A (ko) * | 2021-07-01 | 2024-02-29 | 닝보 티-맥시멈 바이오파마슈티컬스 컴퍼니 리미티드 | B7h3을 표적으로 하는 항원 결합 폴리펩티드 및 이의 응용 |
| CA3227105A1 (en) | 2021-07-30 | 2023-02-02 | Tune Therapeutics, Inc. | Compositions and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) |
| US20240254483A1 (en) | 2021-07-30 | 2024-08-01 | Tune Therapeutics, Inc. | Compositions and methods for modulating expression of frataxin (fxn) |
| WO2023028348A1 (en) | 2021-08-27 | 2023-03-02 | Metagenomi, Inc. | Enzymes with ruvc domains |
| CA3232968A1 (en) | 2021-10-14 | 2023-04-20 | Jasper Williams | Immune cells having co-expressed shrnas and logic gate systems |
| WO2023081900A1 (en) | 2021-11-08 | 2023-05-11 | Juno Therapeutics, Inc. | Engineered t cells expressing a recombinant t cell receptor (tcr) and related systems and methods |
| WO2023115041A1 (en) | 2021-12-17 | 2023-06-22 | Sana Biotechnology, Inc. | Modified paramyxoviridae attachment glycoproteins |
| EP4448549A2 (en) | 2021-12-17 | 2024-10-23 | Sana Biotechnology, Inc. | Modified paramyxoviridae fusion glycoproteins |
| IL313660A (en) | 2021-12-22 | 2024-08-01 | Camp4 Therapeutics Corp | Modulation of gene transcription using antisense oligonucleotides targeting regulatory RNAs |
| EP4463135A2 (en) | 2022-01-10 | 2024-11-20 | Sana Biotechnology, Inc. | Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses |
| EP4463548A1 (en) | 2022-01-14 | 2024-11-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for programming t cell phenotypes through targeted gene activation |
| EP4463549A2 (en) | 2022-01-14 | 2024-11-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for programming t cell phenotypes through targeted gene repression |
| US20250152709A1 (en) | 2022-02-01 | 2025-05-15 | Sana Biotechnology, Inc. | Cd3-targeted lentiviral vectors and uses thereof |
| US20250144235A1 (en) | 2022-02-02 | 2025-05-08 | Sana Biotechnology, Inc. | Methods of repeat dosing and administration of lipid particles or viral vectors and related systems and uses |
| WO2023250511A2 (en) | 2022-06-24 | 2023-12-28 | Tune Therapeutics, Inc. | Compositions, systems, and methods for reducing low-density lipoprotein through targeted gene repression |
| GB202209518D0 (en) | 2022-06-29 | 2022-08-10 | Snipr Biome Aps | Treating & preventing E coli infections |
| CA3261865A1 (en) | 2022-07-12 | 2024-01-18 | Tune Therapeutics Inc | TARGETED TRANSCRIPTIONAL ACTIVATION COMPOSITIONS, SYSTEMS AND METHODS |
| CN115947861B (zh) * | 2022-07-25 | 2023-11-17 | 南京佰抗生物科技有限公司 | 一种高效杂交瘤融合方法 |
| CA3264214A1 (en) | 2022-08-19 | 2024-02-22 | Tune Therapeutics Inc | Compositions, systems and methods of regulating the hepatitis B virus by targeted gene suppression |
| WO2024044655A1 (en) | 2022-08-24 | 2024-02-29 | Sana Biotechnology, Inc. | Delivery of heterologous proteins |
| JP2025531850A (ja) | 2022-09-08 | 2025-09-25 | ジュノー セラピューティクス インコーポレイテッド | T細胞療法および継続的または間欠的dgk阻害剤投薬の組合せ |
| CN120239746A (zh) | 2022-09-19 | 2025-07-01 | 图恩疗法股份有限公司 | 用于调节t细胞功能的组合物、系统和方法 |
| EP4590688A1 (en) | 2022-09-21 | 2025-07-30 | Sana Biotechnology, Inc. | Lipid particles comprising variant paramyxovirus attachment glycoproteins and uses thereof |
| EP4602174A1 (en) | 2022-10-13 | 2025-08-20 | Sana Biotechnology, Inc. | Viral particles targeting hematopoietic stem cells |
| WO2024100604A1 (en) | 2022-11-09 | 2024-05-16 | Juno Therapeutics Gmbh | Methods for manufacturing engineered immune cells |
| EP4627096A1 (en) | 2022-12-02 | 2025-10-08 | Sana Biotechnology, Inc. | Lipid particles with cofusogens and methods of producing and using the same |
| WO2024163683A2 (en) | 2023-02-01 | 2024-08-08 | Tune Therapeutics, Inc. | Systems, compositions, and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) and x-inactive specific transcript (xist) |
| WO2024163678A2 (en) | 2023-02-01 | 2024-08-08 | Tune Therapeutics, Inc. | Fusion proteins and systems for targeted activation of frataxin (fxn) and related methods |
| EP4658675A1 (en) | 2023-02-03 | 2025-12-10 | C3S2 GmbH | Methods for non-viral manufacturing of engineered immune cells |
| TW202442689A (zh) | 2023-03-03 | 2024-11-01 | 美商亞森諾生物科學公司 | 靶向psma及ca9之系統 |
| WO2024220598A2 (en) | 2023-04-18 | 2024-10-24 | Sana Biotechnology, Inc. | Lentiviral vectors with two or more genomes |
| WO2024220560A1 (en) | 2023-04-18 | 2024-10-24 | Sana Biotechnology, Inc. | Engineered protein g fusogens and related lipid particles and methods thereof |
| WO2024220574A1 (en) | 2023-04-18 | 2024-10-24 | Sana Biotechnology, Inc. | Universal protein g fusogens and adapter systems thereof and related lipid particles and uses |
| AU2024274792A1 (en) | 2023-05-23 | 2025-10-23 | Sana Biotechnology, Inc. | Tandem fusogens and related lipid particles |
| WO2025029840A1 (en) | 2023-07-31 | 2025-02-06 | Tune Therapeutics, Inc. | Compositions and methods for multiplexed activation and repression of t cell gene expression |
| WO2025029835A1 (en) | 2023-07-31 | 2025-02-06 | Tune Therapeutics, Inc. | Compositions and methods for modulating il-2 gene expression |
| WO2025038494A1 (en) | 2023-08-11 | 2025-02-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for lymphoid cell differentiation using targeted gene activation |
| WO2025054202A1 (en) | 2023-09-05 | 2025-03-13 | Sana Biotechnology, Inc. | Method of screening a sample comprising a transgene with a unique barcode |
| WO2025059073A1 (en) | 2023-09-11 | 2025-03-20 | Tune Therapeutics, Inc. | Epigenetic editing methods and systems for differentiating stem cells |
| WO2025137646A1 (en) | 2023-12-22 | 2025-06-26 | Recode Therapeutics, Inc. | Gene editing methods and compositions for treating cystic fibrosis |
| WO2025151838A1 (en) | 2024-01-12 | 2025-07-17 | Sana Biotechnology, Inc. | Safety switches to control in vitro and in vivo proliferation of cell therapy products |
| WO2025184529A1 (en) | 2024-03-01 | 2025-09-04 | Sana Biotechnology, Inc. | Viral particles with fusogen display and related compositions and methods |
| US20250345431A1 (en) | 2024-05-10 | 2025-11-13 | Juno Therapeutics, Inc. | Genetically engineered t cells expressing a cd19 chimeric antigen receptor (car) and uses thereof for allogeneic cell therapy |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4690915A (en) | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
| IN165717B (enExample) | 1986-08-07 | 1989-12-23 | Battelle Memorial Institute | |
| US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
| US5827642A (en) | 1994-08-31 | 1998-10-27 | Fred Hutchinson Cancer Research Center | Rapid expansion method ("REM") for in vitro propagation of T lymphocytes |
| WO1996013593A2 (en) | 1994-10-26 | 1996-05-09 | Procept, Inc. | Soluble single chain t cell receptors |
| WO1996018105A1 (en) | 1994-12-06 | 1996-06-13 | The President And Fellows Of Harvard College | Single chain t-cell receptor |
| DE19608753C1 (de) | 1996-03-06 | 1997-06-26 | Medigene Gmbh | Transduktionssystem und seine Verwendung |
| WO1997034634A1 (en) | 1996-03-20 | 1997-09-25 | Sloan-Kettering Institute For Cancer Research | Single chain fv constructs of anti-ganglioside gd2 antibodies |
| ATE533784T1 (de) | 1997-10-02 | 2011-12-15 | Altor Bioscience Corp | Lösliche, einzelkettige proteine des t- zellrezeptors |
| DK1066380T3 (da) | 1998-05-19 | 2002-01-28 | Avidex Ltd | Opløselig T-cellereceptor |
| WO2000014257A1 (en) | 1998-09-04 | 2000-03-16 | Sloan-Kettering Institute For Cancer Research | Fusion receptors specific for prostate-specific membrane antigen and uses thereof |
| AU2472400A (en) | 1998-10-20 | 2000-05-08 | City Of Hope | CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies |
| WO2001094944A2 (en) | 2000-06-02 | 2001-12-13 | Memorial Sloan-Kettering Cancer Center | Artificial antigen presenting cells and methods of use thereof |
| EP1334188B1 (en) | 2000-11-07 | 2006-08-30 | City of Hope | Cd19-specific redirected immune cells |
| US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
| US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
| US20030170238A1 (en) | 2002-03-07 | 2003-09-11 | Gruenberg Micheal L. | Re-activated T-cells for adoptive immunotherapy |
| US7074596B2 (en) | 2002-03-25 | 2006-07-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Synthesis and use of anti-reverse mRNA cap analogues |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| US7569664B2 (en) | 2002-10-09 | 2009-08-04 | Immunocore Limited | Single chain recombinant T cell receptors |
| US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
| JP5563194B2 (ja) | 2004-06-29 | 2014-07-30 | イムノコア リミテッド | 改変t細胞レセプターを発現する細胞 |
| JP2008514685A (ja) | 2004-10-01 | 2008-05-08 | メディジーン リミテッド | 治療剤に連結した、非天然型ジスルフィド鎖間結合を含有するt細胞レセプター |
| US8304529B2 (en) | 2006-07-28 | 2012-11-06 | Life Technologies Corporation | Dinucleotide MRNA cap analogs |
| PT2856876T (pt) | 2007-03-30 | 2018-03-28 | Memorial Sloan Kettering Cancer Center | Expressão constitutiva de ligantes co-estimulatórios em linfócitos t adotivamente transferidos |
| SI2167523T1 (sl) | 2007-06-19 | 2014-09-30 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Sinteza in uporaba anti-reverznih fosforotioatnih analogov kape obveščevalne RNA |
| US8479118B2 (en) | 2007-12-10 | 2013-07-02 | Microsoft Corporation | Switching search providers within a browser search box |
| JP5173594B2 (ja) | 2008-05-27 | 2013-04-03 | キヤノン株式会社 | 管理装置、画像形成装置及びそれらの処理方法 |
| PL215513B1 (pl) | 2008-06-06 | 2013-12-31 | Univ Warszawski | Nowe boranofosforanowe analogi dinukleotydów, ich zastosowanie, czasteczka RNA, sposób otrzymywania RNA oraz sposób otrzymywania peptydów lub bialka |
| US10464987B2 (en) | 2009-10-06 | 2019-11-05 | Abbvie Inc. | Human single-chain T cell receptors |
| ES2911246T3 (es) | 2009-11-03 | 2022-05-18 | Hope City | Receptor del factor de crecimiento epidérmico truncado (EGFRT) para selección de células T transducidas |
| US8956828B2 (en) * | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| KR101976882B1 (ko) | 2011-03-23 | 2019-05-09 | 프레드 헛친슨 켄서 리서치 센터 | 세포 면역요법용 방법 및 조성물 |
| US8398282B2 (en) | 2011-05-12 | 2013-03-19 | Delphi Technologies, Inc. | Vehicle front lighting assembly and systems having a variable tint electrowetting element |
| WO2013059475A1 (en) | 2011-10-18 | 2013-04-25 | Life Technologies Corporation | Alkynyl-derivatized cap analogs, preparation and uses thereof |
| JP6368243B2 (ja) | 2011-11-11 | 2018-08-08 | フレッド ハッチンソン キャンサー リサーチ センター | がんのためのサイクリンa1に標的化されたt細胞免疫療法 |
| JP6850528B2 (ja) | 2012-02-13 | 2021-03-31 | シアトル チルドレンズ ホスピタル ドゥーイング ビジネス アズ シアトル チルドレンズ リサーチ インスティテュート | 二重特異性キメラ抗原受容体およびその治療的使用 |
| 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 |
| RU2665548C2 (ru) | 2012-05-03 | 2018-08-30 | Фред Хатчинсон Кансэр Рисёч Сентер | Способ получения клеток, экспрессирующих т-клеточный рецептор |
| PL2884999T3 (pl) | 2012-08-20 | 2021-07-05 | Fred Hutchinson Cancer Research Center | Sposób i kompozycje do immunoterapii komórkowej |
| RU2729401C2 (ru) | 2012-10-02 | 2020-08-06 | Мемориал Слоан-Кеттеринг Кэнсер Сентер | Композиции и способы для иммунотерапии |
| ES2824024T3 (es) * | 2012-10-10 | 2021-05-11 | Sangamo Therapeutics Inc | Compuestos modificadores de células T y usos de los mismos |
| PT3363902T (pt) * | 2012-12-06 | 2019-12-19 | Sigma Aldrich Co Llc | Modificação e regulação de genoma baseadas em crispr |
| US9405601B2 (en) | 2012-12-20 | 2016-08-02 | Mitsubishi Electric Corporation | In-vehicle apparatus and program |
| AU2014265331B2 (en) * | 2013-05-15 | 2019-12-05 | Sangamo Therapeutics, Inc. | Methods and compositions for treatment of a genetic condition |
| DK3004337T3 (da) * | 2013-05-29 | 2017-11-13 | Cellectis | Fremgangsmåde til konstruktion af T-celler til immunoterapi ved brug af RNA-guidet Cas nuklease-system |
| US9108442B2 (en) | 2013-08-20 | 2015-08-18 | Ricoh Company, Ltd. | Image forming apparatus |
| JP6673838B2 (ja) * | 2014-02-14 | 2020-04-01 | セレクティスCellectis | 免疫細胞と病的細胞の両方に存在する抗原を標的とするように操作された、免疫療法のための細胞 |
| WO2015161276A2 (en) * | 2014-04-18 | 2015-10-22 | Editas Medicine, Inc. | Crispr-cas-related methods, compositions and components for cancer immunotherapy |
| EP3294885B1 (en) * | 2015-05-08 | 2020-07-01 | CureVac Real Estate GmbH | Method for producing rna |
-
2017
- 2017-05-06 SG SG11201809710RA patent/SG11201809710RA/en unknown
- 2017-05-06 AU AU2017261380A patent/AU2017261380A1/en not_active Abandoned
- 2017-05-06 CN CN202310134680.5A patent/CN116850305A/zh active Pending
- 2017-05-06 MX MX2018013445A patent/MX2018013445A/es unknown
- 2017-05-06 JP JP2018558288A patent/JP2019517788A/ja active Pending
- 2017-05-06 KR KR1020237007206A patent/KR20230038299A/ko not_active Ceased
- 2017-05-06 CA CA3022611A patent/CA3022611A1/en active Pending
- 2017-05-06 KR KR1020187035454A patent/KR20190038479A/ko not_active Ceased
- 2017-05-06 MA MA044869A patent/MA44869A/fr unknown
- 2017-05-06 IL IL262772A patent/IL262772B2/en unknown
- 2017-05-06 WO PCT/US2017/031464 patent/WO2017193107A2/en not_active Ceased
- 2017-05-06 CN CN201780042579.XA patent/CN109843915B/zh active Active
- 2017-05-06 US US16/098,845 patent/US20190136230A1/en active Pending
- 2017-05-06 IL IL302641A patent/IL302641A/en unknown
- 2017-05-06 EP EP17726740.8A patent/EP3452499A2/en active Pending
-
2018
- 2018-11-01 MX MX2024000218A patent/MX2024000218A/es unknown
-
2022
- 2022-07-28 JP JP2022120160A patent/JP2023061884A/ja active Pending
- 2022-08-09 AU AU2022215269A patent/AU2022215269A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| IL262772B1 (en) | 2023-06-01 |
| MA44869A (fr) | 2019-03-13 |
| EP3452499A2 (en) | 2019-03-13 |
| MX2024000218A (es) | 2024-01-30 |
| IL262772A (en) | 2018-12-31 |
| CN116850305A (zh) | 2023-10-10 |
| KR20190038479A (ko) | 2019-04-08 |
| WO2017193107A2 (en) | 2017-11-09 |
| IL302641A (en) | 2023-07-01 |
| IL262772B2 (en) | 2023-10-01 |
| AU2022215269A1 (en) | 2022-11-17 |
| CN109843915B (zh) | 2023-03-03 |
| US20190136230A1 (en) | 2019-05-09 |
| JP2023061884A (ja) | 2023-05-02 |
| AU2017261380A1 (en) | 2018-11-22 |
| CN109843915A (zh) | 2019-06-04 |
| JP2019517788A (ja) | 2019-06-27 |
| SG11201809710RA (en) | 2018-11-29 |
| MX2018013445A (es) | 2019-09-09 |
| KR20230038299A (ko) | 2023-03-17 |
| WO2017193107A3 (en) | 2018-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109843915B (zh) | 基因工程化细胞及其制备方法 | |
| AU2021282533C1 (en) | Optimized crispr/cas9 systems and methods for gene editing in stem cells | |
| US20250320491A1 (en) | Crispr-cpf1-related methods, compositions and components for cancer immunotherapy | |
| US11952408B2 (en) | HPV-specific binding molecules | |
| AU2018358250B2 (en) | Methods, compositions and components for CRISPR-CAS9 editing of TGFBR2 in T cells for immunotherapy | |
| JP2022081522A (ja) | がん免疫療法のためのcrispr-cas関連方法、組成物および構成要素 | |
| KR102796744B1 (ko) | 이식의 개선을 위한 crispr/cas-관련 방법 및 조성물 | |
| US20180112213A1 (en) | Crispr/cas-related methods, compositions and components | |
| KR20200133219A (ko) | 개선된 면역요법을 위한 유전자-조절 조성물 및 방법 | |
| JP2022531577A (ja) | 改変されたcd247遺伝子座からキメラ受容体を発現する細胞、関連ポリヌクレオチド、および方法 | |
| CN116802203A (zh) | 从经修饰的恒定cd3免疫球蛋白超家族链基因座表达嵌合受体的细胞、相关多核苷酸和方法 | |
| KR20250174987A (ko) | 개선된 면역요법을 위한 유전자-조절 조성물 및 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220502 |
|
| EEER | Examination request |
Effective date: 20220502 |
|
| EEER | Examination request |
Effective date: 20220502 |
|
| EEER | Examination request |
Effective date: 20220502 |
|
| EEER | Examination request |
Effective date: 20220502 |