AU2022325232A1 - Genetically modified primary cells for allogeneic cell therapy - Google Patents
Genetically modified primary cells for allogeneic cell therapy Download PDFInfo
- Publication number
- AU2022325232A1 AU2022325232A1 AU2022325232A AU2022325232A AU2022325232A1 AU 2022325232 A1 AU2022325232 A1 AU 2022325232A1 AU 2022325232 A AU2022325232 A AU 2022325232A AU 2022325232 A AU2022325232 A AU 2022325232A AU 2022325232 A1 AU2022325232 A1 AU 2022325232A1
- Authority
- AU
- Australia
- Prior art keywords
- cell
- cells
- expression
- engineered
- hla
- 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
- 238000011129 allogeneic cell therapy Methods 0.000 title abstract description 4
- 230000004048 modification Effects 0.000 claims abstract description 185
- 238000012986 modification Methods 0.000 claims abstract description 185
- 210000004027 cell Anatomy 0.000 claims description 896
- 230000014509 gene expression Effects 0.000 claims description 460
- 238000000034 method Methods 0.000 claims description 395
- 210000004153 islets of langerhan Anatomy 0.000 claims description 293
- 108090000623 proteins and genes Proteins 0.000 claims description 272
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims description 177
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims description 177
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 claims description 134
- 101710197836 HLA class I histocompatibility antigen, alpha chain G Proteins 0.000 claims description 113
- 102000004169 proteins and genes Human genes 0.000 claims description 108
- 230000003614 tolerogenic effect Effects 0.000 claims description 94
- 102000040430 polynucleotide Human genes 0.000 claims description 88
- 108091033319 polynucleotide Proteins 0.000 claims description 88
- 239000002157 polynucleotide Substances 0.000 claims description 88
- 108091054437 MHC class I family Proteins 0.000 claims description 82
- 108091054438 MHC class II family Proteins 0.000 claims description 82
- 239000003153 chemical reaction reagent Substances 0.000 claims description 72
- 230000033001 locomotion Effects 0.000 claims description 71
- 230000002829 reductive effect Effects 0.000 claims description 67
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 claims description 65
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 claims description 65
- 239000003018 immunosuppressive agent Substances 0.000 claims description 61
- 229940125721 immunosuppressive agent Drugs 0.000 claims description 59
- 230000001965 increasing effect Effects 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 52
- 101710163270 Nuclease Proteins 0.000 claims description 51
- 101150076800 B2M gene Proteins 0.000 claims description 49
- 238000010362 genome editing Methods 0.000 claims description 47
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 claims description 46
- 206010012601 diabetes mellitus Diseases 0.000 claims description 46
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 45
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 45
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
- -1 HLA- DM Proteins 0.000 claims description 44
- 101100382122 Homo sapiens CIITA gene Proteins 0.000 claims description 41
- 102000043131 MHC class II family Human genes 0.000 claims description 41
- 230000001404 mediated effect Effects 0.000 claims description 41
- 206010010144 Completed suicide Diseases 0.000 claims description 39
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims description 39
- 201000010099 disease Diseases 0.000 claims description 39
- 230000002779 inactivation Effects 0.000 claims description 39
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims description 39
- 230000000735 allogeneic effect Effects 0.000 claims description 38
- 102000043129 MHC class I family Human genes 0.000 claims description 37
- 108700028369 Alleles Proteins 0.000 claims description 33
- 102100030886 Complement receptor type 1 Human genes 0.000 claims description 32
- 101000727061 Homo sapiens Complement receptor type 1 Proteins 0.000 claims description 32
- 238000003780 insertion Methods 0.000 claims description 31
- 230000037431 insertion Effects 0.000 claims description 31
- 210000000130 stem cell Anatomy 0.000 claims description 30
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 claims description 28
- 108010052199 HLA-C Antigens Proteins 0.000 claims description 28
- 239000000725 suspension Substances 0.000 claims description 28
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 27
- 102100022002 CD59 glycoprotein Human genes 0.000 claims description 26
- 102100025680 Complement decay-accelerating factor Human genes 0.000 claims description 26
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 claims description 26
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 claims description 26
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 claims description 26
- 102100039373 Membrane cofactor protein Human genes 0.000 claims description 26
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 claims description 25
- 102100038081 Signal transducer CD24 Human genes 0.000 claims description 25
- 230000001939 inductive effect Effects 0.000 claims description 25
- 102000004039 Caspase-9 Human genes 0.000 claims description 24
- 108090000566 Caspase-9 Proteins 0.000 claims description 24
- 239000013598 vector Substances 0.000 claims description 24
- 102000015789 HLA-DP Antigens Human genes 0.000 claims description 23
- 108010010378 HLA-DP Antigens Proteins 0.000 claims description 23
- 108010062347 HLA-DQ Antigens Proteins 0.000 claims description 23
- 108010058597 HLA-DR Antigens Proteins 0.000 claims description 23
- 102000006354 HLA-DR Antigens Human genes 0.000 claims description 23
- 101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 claims description 23
- 102100037589 OX-2 membrane glycoprotein Human genes 0.000 claims description 23
- 210000002889 endothelial cell Anatomy 0.000 claims description 23
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 22
- AVVWPBAENSWJCB-GASJEMHNSA-N D-mannofuranose Chemical compound OC[C@@H](O)[C@H]1OC(O)[C@@H](O)[C@H]1O AVVWPBAENSWJCB-GASJEMHNSA-N 0.000 claims description 21
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 claims description 21
- 108010075704 HLA-A Antigens Proteins 0.000 claims description 21
- 108010058607 HLA-B Antigens Proteins 0.000 claims description 21
- 108010024164 HLA-G Antigens Proteins 0.000 claims description 21
- 101000616876 Homo sapiens Mesencephalic astrocyte-derived neurotrophic factor Proteins 0.000 claims description 21
- 102100021833 Mesencephalic astrocyte-derived neurotrophic factor Human genes 0.000 claims description 21
- 108700019146 Transgenes Proteins 0.000 claims description 21
- 102100036846 C-C motif chemokine 21 Human genes 0.000 claims description 20
- 108010080611 Cytosine Deaminase Proteins 0.000 claims description 20
- 102000000311 Cytosine Deaminase Human genes 0.000 claims description 20
- 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 claims description 20
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 20
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 20
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 claims description 19
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 claims description 19
- 230000001413 cellular effect Effects 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 210000004927 skin cell Anatomy 0.000 claims description 19
- 210000001685 thyroid gland Anatomy 0.000 claims description 19
- 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 claims description 18
- 210000003494 hepatocyte Anatomy 0.000 claims description 18
- 230000002207 retinal effect Effects 0.000 claims description 18
- 108091033409 CRISPR Proteins 0.000 claims description 17
- 108020004414 DNA Proteins 0.000 claims description 17
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 claims description 17
- 210000004369 blood Anatomy 0.000 claims description 17
- 239000008280 blood Substances 0.000 claims description 17
- 230000007812 deficiency Effects 0.000 claims description 17
- 210000000981 epithelium Anatomy 0.000 claims description 17
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 16
- 101001034314 Homo sapiens Lactadherin Proteins 0.000 claims description 16
- 101000836075 Homo sapiens Serpin B9 Proteins 0.000 claims description 16
- 102100039648 Lactadherin Human genes 0.000 claims description 16
- 102100025517 Serpin B9 Human genes 0.000 claims description 16
- 238000010459 TALEN Methods 0.000 claims description 16
- 238000002659 cell therapy Methods 0.000 claims description 16
- 239000008103 glucose Substances 0.000 claims description 16
- 230000002147 killing effect Effects 0.000 claims description 16
- 230000003068 static effect Effects 0.000 claims description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 210000002540 macrophage Anatomy 0.000 claims description 15
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 14
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 14
- 108010081734 Ribonucleoproteins Proteins 0.000 claims description 14
- 102000004389 Ribonucleoproteins Human genes 0.000 claims description 14
- 210000005260 human cell Anatomy 0.000 claims description 14
- 230000010354 integration Effects 0.000 claims description 14
- 210000000822 natural killer cell Anatomy 0.000 claims description 14
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 14
- 229960002930 sirolimus Drugs 0.000 claims description 14
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 14
- 101150089023 FASLG gene Proteins 0.000 claims description 13
- 108020005004 Guide RNA Proteins 0.000 claims description 13
- 108010047933 Tumor Necrosis Factor alpha-Induced Protein 3 Proteins 0.000 claims description 13
- 102100024596 Tumor necrosis factor alpha-induced protein 3 Human genes 0.000 claims description 13
- 238000012217 deletion Methods 0.000 claims description 13
- 230000037430 deletion Effects 0.000 claims description 13
- 101000991060 Homo sapiens MHC class I polypeptide-related sequence A Proteins 0.000 claims description 12
- 102100031344 Thioredoxin-interacting protein Human genes 0.000 claims description 12
- 101710114149 Thioredoxin-interacting protein Proteins 0.000 claims description 12
- 230000030833 cell death Effects 0.000 claims description 12
- 230000007423 decrease Effects 0.000 claims description 12
- 230000028993 immune response Effects 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- 230000008685 targeting Effects 0.000 claims description 11
- 108010076667 Caspases Proteins 0.000 claims description 10
- 102000011727 Caspases Human genes 0.000 claims description 10
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 claims description 10
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 claims description 10
- 101000979565 Homo sapiens Protein NLRC5 Proteins 0.000 claims description 10
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 10
- 102100023432 Protein NLRC5 Human genes 0.000 claims description 10
- 102000006601 Thymidine Kinase Human genes 0.000 claims description 10
- 108020004440 Thymidine kinase Proteins 0.000 claims description 10
- 230000004075 alteration Effects 0.000 claims description 10
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 10
- 210000000601 blood cell Anatomy 0.000 claims description 10
- 210000002865 immune cell Anatomy 0.000 claims description 10
- 238000011534 incubation Methods 0.000 claims description 10
- 238000002054 transplantation Methods 0.000 claims description 10
- 102100027207 CD27 antigen Human genes 0.000 claims description 9
- 102100020986 DNA-binding protein RFX5 Human genes 0.000 claims description 9
- 102100021044 DNA-binding protein RFXANK Human genes 0.000 claims description 9
- 102100031546 HLA class II histocompatibility antigen, DO beta chain Human genes 0.000 claims description 9
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 9
- 101001075432 Homo sapiens DNA-binding protein RFX5 Proteins 0.000 claims description 9
- 101001075464 Homo sapiens DNA-binding protein RFXANK Proteins 0.000 claims description 9
- 101000866281 Homo sapiens HLA class II histocompatibility antigen, DO beta chain Proteins 0.000 claims description 9
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 claims description 9
- 101001075466 Homo sapiens Regulatory factor X-associated protein Proteins 0.000 claims description 9
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 claims description 9
- 102100021043 Regulatory factor X-associated protein Human genes 0.000 claims description 9
- 150000001413 amino acids Chemical class 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 231100000221 frame shift mutation induction Toxicity 0.000 claims description 9
- 230000037433 frameshift Effects 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 241001529453 unidentified herpesvirus Species 0.000 claims description 9
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 8
- 241000701022 Cytomegalovirus Species 0.000 claims description 8
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 claims description 8
- 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 8
- 108010074328 Interferon-gamma Proteins 0.000 claims description 8
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 8
- 102100037499 Parkinson disease protein 7 Human genes 0.000 claims description 8
- 108010032428 Protein Deglycase DJ-1 Proteins 0.000 claims description 8
- 241000714474 Rous sarcoma virus Species 0.000 claims description 8
- 230000006907 apoptotic process Effects 0.000 claims description 8
- 208000019423 liver disease Diseases 0.000 claims description 8
- 108020004999 messenger RNA Proteins 0.000 claims description 8
- 230000001590 oxidative effect Effects 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 102100024217 CAMPATH-1 antigen Human genes 0.000 claims description 7
- 108010065524 CD52 Antigen Proteins 0.000 claims description 7
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 108010039471 Fas Ligand Protein Proteins 0.000 claims description 7
- 101150105660 MFGE8 gene Proteins 0.000 claims description 7
- 230000004913 activation Effects 0.000 claims description 7
- 210000004102 animal cell Anatomy 0.000 claims description 7
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 claims description 7
- 230000003914 insulin secretion Effects 0.000 claims description 7
- 238000010255 intramuscular injection Methods 0.000 claims description 7
- 230000031942 natural killer cell mediated cytotoxicity Effects 0.000 claims description 7
- 241000283690 Bos taurus Species 0.000 claims description 6
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 6
- 102100021158 Double homeobox protein 4 Human genes 0.000 claims description 6
- 102000001301 EGF receptor Human genes 0.000 claims description 6
- 102100035833 Histo-blood group ABO system transferase Human genes 0.000 claims description 6
- 101000968549 Homo sapiens Double homeobox protein 4 Proteins 0.000 claims description 6
- 101000802660 Homo sapiens Histo-blood group ABO system transferase Proteins 0.000 claims description 6
- 102000003814 Interleukin-10 Human genes 0.000 claims description 6
- 108090000174 Interleukin-10 Proteins 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 claims description 6
- 102000008579 Transposases Human genes 0.000 claims description 6
- 108010020764 Transposases Proteins 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 230000000295 complement effect Effects 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 208000021921 corneal disease Diseases 0.000 claims description 6
- 239000002577 cryoprotective agent Substances 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 6
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 6
- 230000002518 glial effect Effects 0.000 claims description 6
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 6
- 230000001976 improved effect Effects 0.000 claims description 6
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 6
- 239000010445 mica Substances 0.000 claims description 6
- 229910052618 mica group Inorganic materials 0.000 claims description 6
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims description 5
- 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 claims description 5
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 claims description 5
- 101001012447 Homo sapiens Ectonucleoside triphosphate diphosphohydrolase 1 Proteins 0.000 claims description 5
- 101000598002 Homo sapiens Interferon regulatory factor 1 Proteins 0.000 claims description 5
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 claims description 5
- 102100036981 Interferon regulatory factor 1 Human genes 0.000 claims description 5
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 210000004986 primary T-cell Anatomy 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 5
- 239000013603 viral vector Substances 0.000 claims description 5
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 4
- 108010088751 Albumins Proteins 0.000 claims description 4
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 claims description 4
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 101150017501 CCR5 gene Proteins 0.000 claims description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 4
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 4
- 101150066398 CXCR4 gene Proteins 0.000 claims description 4
- 101150055030 Clybl gene Proteins 0.000 claims description 4
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 4
- 108010036949 Cyclosporine Proteins 0.000 claims description 4
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 4
- 102000006395 Globulins Human genes 0.000 claims description 4
- 108010044091 Globulins Proteins 0.000 claims description 4
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 4
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 4
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 claims description 4
- 101000763322 Homo sapiens M1-specific T cell receptor beta chain Proteins 0.000 claims description 4
- 101000996109 Homo sapiens Neuroligin-4, Y-linked Proteins 0.000 claims description 4
- 101000613375 Homo sapiens Protocadherin-11 Y-linked Proteins 0.000 claims description 4
- 101000763321 Homo sapiens T cell receptor beta chain MC.7.G5 Proteins 0.000 claims description 4
- 101000635804 Homo sapiens Tissue factor Proteins 0.000 claims description 4
- 101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 0.000 claims description 4
- 102100026964 M1-specific T cell receptor beta chain Human genes 0.000 claims description 4
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 claims description 4
- 241000713333 Mouse mammary tumor virus Species 0.000 claims description 4
- 102100034448 Neuroligin-4, Y-linked Human genes 0.000 claims description 4
- 108091000080 Phosphotransferase Proteins 0.000 claims description 4
- 102100040932 Protocadherin-11 Y-linked Human genes 0.000 claims description 4
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 claims description 4
- 102100029452 T cell receptor alpha chain constant Human genes 0.000 claims description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 4
- 102100030859 Tissue factor Human genes 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 241000700618 Vaccinia virus Species 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 4
- 230000001494 anti-thymocyte effect Effects 0.000 claims description 4
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 4
- 229960001265 ciclosporin Drugs 0.000 claims description 4
- 239000003246 corticosteroid Substances 0.000 claims description 4
- 229960004397 cyclophosphamide Drugs 0.000 claims description 4
- 229930182912 cyclosporin Natural products 0.000 claims description 4
- 210000005064 dopaminergic neuron Anatomy 0.000 claims description 4
- 230000003511 endothelial effect Effects 0.000 claims description 4
- 239000012595 freezing medium Substances 0.000 claims description 4
- 210000002064 heart cell Anatomy 0.000 claims description 4
- 230000002519 immonomodulatory effect Effects 0.000 claims description 4
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 4
- 239000007927 intramuscular injection Substances 0.000 claims description 4
- 208000017169 kidney disease Diseases 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- 210000000663 muscle cell Anatomy 0.000 claims description 4
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 4
- 229960004866 mycophenolate mofetil Drugs 0.000 claims description 4
- 210000003061 neural cell Anatomy 0.000 claims description 4
- 102000020233 phosphotransferase Human genes 0.000 claims description 4
- 210000002363 skeletal muscle cell Anatomy 0.000 claims description 4
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 241000701161 unidentified adenovirus Species 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 3
- 101710117545 C protein Proteins 0.000 claims description 3
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 claims description 3
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 claims description 3
- 101150069031 CSN2 gene Proteins 0.000 claims description 3
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 3
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 3
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 3
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 claims description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 3
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 3
- 102100034256 Mucin-1 Human genes 0.000 claims description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 3
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 3
- 230000002457 bidirectional effect Effects 0.000 claims description 3
- 230000027455 binding Effects 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 101150055601 cops2 gene Proteins 0.000 claims description 3
- 230000003013 cytotoxicity Effects 0.000 claims description 3
- 231100000135 cytotoxicity Toxicity 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 230000001506 immunosuppresive effect Effects 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 150000002632 lipids Chemical group 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 230000035899 viability Effects 0.000 claims description 3
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 2
- 101150013553 CD40 gene Proteins 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims description 2
- 201000001925 Fuchs' endothelial dystrophy Diseases 0.000 claims description 2
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 2
- 101100066427 Homo sapiens FCGR1A gene Proteins 0.000 claims description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims description 2
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 claims description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 2
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 claims description 2
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 2
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 2
- 102000004877 Insulin Human genes 0.000 claims description 2
- 108090001061 Insulin Proteins 0.000 claims description 2
- 102100037852 Insulin-like growth factor I Human genes 0.000 claims description 2
- 102100037850 Interferon gamma Human genes 0.000 claims description 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 claims description 2
- 102000010789 Interleukin-2 Receptors Human genes 0.000 claims description 2
- 108090000978 Interleukin-4 Proteins 0.000 claims description 2
- 102000004388 Interleukin-4 Human genes 0.000 claims description 2
- 108010002616 Interleukin-5 Proteins 0.000 claims description 2
- 108090001005 Interleukin-6 Proteins 0.000 claims description 2
- 102000004889 Interleukin-6 Human genes 0.000 claims description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 claims description 2
- 108090001007 Interleukin-8 Proteins 0.000 claims description 2
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 claims description 2
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims description 2
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 208000022873 Ocular disease Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 2
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 2
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 2
- 102400000160 Thymopentin Human genes 0.000 claims description 2
- 101800001703 Thymopentin Proteins 0.000 claims description 2
- 208000024799 Thyroid disease Diseases 0.000 claims description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 238000004115 adherent culture Methods 0.000 claims description 2
- 239000003430 antimalarial agent Substances 0.000 claims description 2
- 229940033495 antimalarials Drugs 0.000 claims description 2
- 229960002170 azathioprine Drugs 0.000 claims description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 2
- 229960000106 biosimilars Drugs 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- PHEZJEYUWHETKO-UHFFFAOYSA-N brequinar Chemical compound N1=C2C=CC(F)=CC2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PHEZJEYUWHETKO-UHFFFAOYSA-N 0.000 claims description 2
- 229950010231 brequinar Drugs 0.000 claims description 2
- 230000006037 cell lysis Effects 0.000 claims description 2
- 229960005395 cetuximab Drugs 0.000 claims description 2
- 230000007882 cirrhosis Effects 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 210000000399 corneal endothelial cell Anatomy 0.000 claims description 2
- 229960001334 corticosteroids Drugs 0.000 claims description 2
- 230000003247 decreasing effect Effects 0.000 claims description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 2
- 210000002919 epithelial cell Anatomy 0.000 claims description 2
- 210000004700 fetal blood Anatomy 0.000 claims description 2
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 210000001368 germline stem cell Anatomy 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 150000002343 gold Chemical class 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 230000002163 immunogen Effects 0.000 claims description 2
- 230000028709 inflammatory response Effects 0.000 claims description 2
- 229940125396 insulin Drugs 0.000 claims description 2
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims description 2
- 229960000681 leflunomide Drugs 0.000 claims description 2
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 201000005243 lung squamous cell carcinoma Diseases 0.000 claims description 2
- 208000003747 lymphoid leukemia Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 210000001939 mature NK cell Anatomy 0.000 claims description 2
- 229960001428 mercaptopurine Drugs 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims description 2
- 229950000844 mizoribine Drugs 0.000 claims description 2
- 229950007699 mogamulizumab Drugs 0.000 claims description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 claims description 2
- 229960000951 mycophenolic acid Drugs 0.000 claims description 2
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
- 229960003347 obinutuzumab Drugs 0.000 claims description 2
- 229950009090 ocaratuzumab Drugs 0.000 claims description 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 2
- 229960004618 prednisone Drugs 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 102000005962 receptors Human genes 0.000 claims description 2
- 108020003175 receptors Proteins 0.000 claims description 2
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 claims description 2
- 229960004641 rituximab Drugs 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims description 2
- 229960001940 sulfasalazine Drugs 0.000 claims description 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims description 2
- 230000001629 suppression Effects 0.000 claims description 2
- 230000008718 systemic inflammatory response Effects 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- PSWFFKRAVBDQEG-YGQNSOCVSA-N thymopentin Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PSWFFKRAVBDQEG-YGQNSOCVSA-N 0.000 claims description 2
- 229960004517 thymopentin Drugs 0.000 claims description 2
- 208000021510 thyroid gland disease Diseases 0.000 claims description 2
- 229940060960 tomuzotuximab Drugs 0.000 claims description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 229950004593 ublituximab Drugs 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 102100026371 MHC class II transactivator Human genes 0.000 claims 13
- 108700002010 MHC class II transactivator Proteins 0.000 claims 13
- 101710153660 Nuclear receptor corepressor 2 Proteins 0.000 claims 5
- 238000010354 CRISPR gene editing Methods 0.000 claims 4
- 102000015212 Fas Ligand Protein Human genes 0.000 claims 3
- 101500028228 Homo sapiens Soluble HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 claims 3
- 102400000958 Soluble HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 claims 3
- 101150056927 F3 gene Proteins 0.000 claims 2
- 101150048676 FUT1 gene Proteins 0.000 claims 2
- 101150021904 HMGB1 gene Proteins 0.000 claims 2
- 101150091012 KDM5D gene Proteins 0.000 claims 2
- 101150108975 Rhd gene Proteins 0.000 claims 2
- 101150099178 abo gene Proteins 0.000 claims 2
- 101150084157 lrp-1 gene Proteins 0.000 claims 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims 1
- 102000000743 Interleukin-5 Human genes 0.000 claims 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 1
- 102100040247 Tumor necrosis factor Human genes 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- 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 1
- 210000001127 pigmented epithelial cell Anatomy 0.000 claims 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 1
- 238000012239 gene modification Methods 0.000 abstract description 8
- 230000005017 genetic modification Effects 0.000 abstract description 7
- 235000013617 genetically modified food Nutrition 0.000 abstract description 7
- 235000018102 proteins Nutrition 0.000 description 54
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 46
- 241000699666 Mus <mouse, genus> Species 0.000 description 34
- 241000699670 Mus sp. Species 0.000 description 24
- 102000008096 B7-H1 Antigen Human genes 0.000 description 20
- 230000022534 cell killing Effects 0.000 description 18
- 108090000765 processed proteins & peptides Proteins 0.000 description 18
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 17
- 102000055647 human CSF2RB Human genes 0.000 description 17
- 102000004196 processed proteins & peptides Human genes 0.000 description 17
- 238000000338 in vitro Methods 0.000 description 16
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 16
- 230000029918 bioluminescence Effects 0.000 description 15
- 238000005415 bioluminescence Methods 0.000 description 15
- 238000005516 engineering process Methods 0.000 description 12
- 238000005259 measurement Methods 0.000 description 11
- 238000011002 quantification Methods 0.000 description 11
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 description 10
- 229940027941 immunoglobulin g Drugs 0.000 description 9
- 230000002018 overexpression Effects 0.000 description 9
- 108060001084 Luciferase Proteins 0.000 description 8
- 239000005089 Luciferase Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 150000007523 nucleic acids Chemical class 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 7
- 238000010453 CRISPR/Cas method Methods 0.000 description 7
- 210000000987 immune system Anatomy 0.000 description 7
- 102000008070 Interferon-gamma Human genes 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 238000011577 humanized mouse model Methods 0.000 description 6
- 229960003130 interferon gamma Drugs 0.000 description 6
- 210000004498 neuroglial cell Anatomy 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 230000002103 transcriptional effect Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 238000006471 dimerization reaction Methods 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108010042407 Endonucleases Proteins 0.000 description 4
- 102000004459 Nitroreductase Human genes 0.000 description 4
- 101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 description 4
- 102000030764 Purine-nucleoside phosphorylase Human genes 0.000 description 4
- 125000000539 amino acid group Chemical class 0.000 description 4
- 230000001640 apoptogenic effect Effects 0.000 description 4
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical group NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 4
- 229960004413 flucytosine Drugs 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 238000010353 genetic engineering Methods 0.000 description 4
- 230000005934 immune activation Effects 0.000 description 4
- 230000008073 immune recognition Effects 0.000 description 4
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 230000001338 necrotic effect Effects 0.000 description 4
- 108020001162 nitroreductase Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000012384 transportation and delivery Methods 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 101000634853 Homo sapiens T cell receptor alpha chain constant Proteins 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 3
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000003044 adaptive effect Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 229960002963 ganciclovir Drugs 0.000 description 3
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical group O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 210000004180 plasmocyte Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 101900095660 Escherichia coli Cytosine deaminase Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 2
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003617 indole-3-acetic acid Substances 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 108091008042 inhibitory receptors Proteins 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- SYMHUEFSSMBHJA-UHFFFAOYSA-N 6-methylpurine Chemical compound CC1=NC=NC2=C1NC=N2 SYMHUEFSSMBHJA-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- NSBGUMKAXUXKGI-BPNHAYRBSA-N AP20187 Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCC(=O)NCC(CNC(=O)COC=2C=C(C=CC=2)[C@@H](CCC=2C=C(OC)C(OC)=CC=2)OC(=O)[C@H]2N(CCCC2)C(=O)[C@@H](CC)C=2C=C(OC)C(OC)=C(OC)C=2)CN(C)C)C=CC=1)CC1=CC=C(OC)C(OC)=C1 NSBGUMKAXUXKGI-BPNHAYRBSA-N 0.000 description 1
- 241001156002 Anthonomus pomorum Species 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000983523 Homo sapiens Caspase-9 Proteins 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 108020003285 Isocitrate lyase Proteins 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710104624 Proline/betaine transporter Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000005497 Thymidylate Synthase Human genes 0.000 description 1
- 102100038313 Transcription factor E2-alpha Human genes 0.000 description 1
- GQLCLPLEEOUJQC-ZTQDTCGGSA-N [(1r)-3-(3,4-dimethoxyphenyl)-1-[3-[2-[2-[[2-[3-[(1r)-3-(3,4-dimethoxyphenyl)-1-[(2s)-1-[(2s)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetyl]amino]ethylamino]-2-oxoethoxy]phenyl]propyl] (2s)-1-[(2s)-2-(3,4,5-trimethoxyph Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCC(=O)NCCNC(=O)COC=2C=C(C=CC=2)[C@@H](CCC=2C=C(OC)C(OC)=CC=2)OC(=O)[C@H]2N(CCCC2)C(=O)[C@@H](CC)C=2C=C(OC)C(OC)=C(OC)C=2)C=CC=1)CC1=CC=C(OC)C(OC)=C1 GQLCLPLEEOUJQC-ZTQDTCGGSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 102000047279 human B2M Human genes 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000033065 inborn errors of immunity Diseases 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000005776 mitochondrial apoptotic pathway Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000007498 myristoylation Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 102200015453 rs121912293 Human genes 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000003981 vehicle 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
- 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
-
- 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
- C12N5/0676—Pancreatic cells
-
- 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
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- 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
- A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
-
- 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
- A61K35/37—Digestive system
- A61K35/39—Pancreas; Islets of Langerhans
-
- 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
- A61K35/37—Digestive system
- A61K35/407—Liver; Hepatocytes
-
- 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
- A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
-
- 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
- A61K35/55—Glands not provided for in groups A61K35/22 - A61K35/545, e.g. thyroids, parathyroids or pineal glands
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
- A61K40/22—Immunosuppressive or immunotolerising
-
- 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
- A61K40/416—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- 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
- 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
- C12N15/1138—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 against receptors or cell surface proteins
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian 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
- 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
- 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
- A61K40/00—Cellular immunotherapy
- A61K40/50—Cellular immunotherapy characterised by the use of allogeneic 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
- 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
- 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
- C12N2527/00—Culture process characterised by the use of mechanical forces, e.g. strain, vibration
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cell Biology (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Developmental Biology & Embryology (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163232161P | 2021-08-11 | 2021-08-11 | |
| US63/232,161 | 2021-08-11 | ||
| US202263297694P | 2022-01-07 | 2022-01-07 | |
| US63/297,694 | 2022-01-07 | ||
| US202263344502P | 2022-05-20 | 2022-05-20 | |
| US63/344,502 | 2022-05-20 | ||
| US202263348990P | 2022-06-03 | 2022-06-03 | |
| US63/348,990 | 2022-06-03 | ||
| US202263353531P | 2022-06-17 | 2022-06-17 | |
| US63/353,531 | 2022-06-17 | ||
| PCT/US2022/074878 WO2023019229A1 (en) | 2021-08-11 | 2022-08-11 | Genetically modified primary cells for allogeneic cell therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2022325232A1 true AU2022325232A1 (en) | 2024-02-08 |
Family
ID=83692683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2022325232A Pending AU2022325232A1 (en) | 2021-08-11 | 2022-08-11 | Genetically modified primary cells for allogeneic cell therapy |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20240010988A1 (https=) |
| EP (1) | EP4384189A1 (https=) |
| JP (1) | JP2024531234A (https=) |
| KR (1) | KR20240073006A (https=) |
| AU (1) | AU2022325232A1 (https=) |
| CA (1) | CA3227108A1 (https=) |
| IL (1) | IL310691A (https=) |
| MX (1) | MX2024001208A (https=) |
| WO (1) | WO2023019229A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW202245598A (zh) * | 2021-02-09 | 2022-12-01 | 美商千禧製藥公司 | 用於冷凍及解凍哺乳動物細胞的方法及組成物 |
| AU2024264889A1 (en) * | 2023-05-03 | 2025-11-13 | Sana Biotechnology, Inc. | Methods of dosing and administration of engineered islet cells |
| WO2025047921A1 (ja) * | 2023-09-01 | 2025-03-06 | 株式会社セル―ジョン | 拒絶反応に対する回避方法 |
Family Cites Families (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8724885D0 (en) | 1987-10-23 | 1987-11-25 | Binns M M | Fowlpox virus promotors |
| US5674722A (en) | 1987-12-11 | 1997-10-07 | Somatix Therapy Corporation | Genetic modification of endothelial cells |
| US5420032A (en) | 1991-12-23 | 1995-05-30 | Universitge Laval | Homing endonuclease which originates from chlamydomonas eugametos and recognizes and cleaves a 15, 17 or 19 degenerate double stranded nucleotide sequence |
| US5792632A (en) | 1992-05-05 | 1998-08-11 | Institut Pasteur | Nucleotide sequence encoding the enzyme I-SceI and the uses thereof |
| DE4228458A1 (de) | 1992-08-27 | 1994-06-01 | Beiersdorf Ag | Multicistronische Expressionseinheiten und deren Verwendung |
| US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
| DE19539493A1 (de) | 1995-10-24 | 1997-04-30 | Thomae Gmbh Dr K | Starker homologer Promotor aus Hamster |
| GB9526131D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Recombinant chimeric receptors |
| WO1998011244A2 (en) | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Aav4 vector and uses thereof |
| US7541034B1 (en) | 1997-03-20 | 2009-06-02 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant antibodies and immunoconjugates targeted to CD-22 bearing cells and tumors |
| GB9710807D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| GB9710809D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| US6156303A (en) | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
| US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
| US6140081A (en) | 1998-10-16 | 2000-10-31 | The Scripps Research Institute | Zinc finger binding domains for GNN |
| US6599692B1 (en) | 1999-09-14 | 2003-07-29 | Sangamo Bioscience, Inc. | Functional genomics using zinc finger proteins |
| US7070934B2 (en) | 1999-01-12 | 2006-07-04 | Sangamo Biosciences, Inc. | Ligand-controlled regulation of endogenous gene expression |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US6794136B1 (en) | 2000-11-20 | 2004-09-21 | Sangamo Biosciences, Inc. | Iterative optimization in the design of binding proteins |
| US7030215B2 (en) | 1999-03-24 | 2006-04-18 | Sangamo Biosciences, Inc. | Position dependent recognition of GNN nucleotide triplets by zinc fingers |
| AU776576B2 (en) | 1999-12-06 | 2004-09-16 | Sangamo Biosciences, Inc. | Methods of using randomized libraries of zinc finger proteins for the identification of gene function |
| US6689558B2 (en) | 2000-02-08 | 2004-02-10 | Sangamo Biosciences, Inc. | Cells for drug discovery |
| JP2002060786A (ja) | 2000-08-23 | 2002-02-26 | Kao Corp | 硬質表面用殺菌防汚剤 |
| US7575924B2 (en) | 2000-11-13 | 2009-08-18 | Research Development Foundation | Methods and compositions relating to improved lentiviral vectors and their applications |
| US7067317B2 (en) | 2000-12-07 | 2006-06-27 | Sangamo Biosciences, Inc. | Regulation of angiogenesis with zinc finger proteins |
| ATE437221T1 (de) | 2001-05-14 | 2009-08-15 | Gbp Ip Llc | Lentivirale vektoren kodierend für gerinnungsfaktoren für die gentherapie |
| ATE527347T1 (de) | 2001-08-02 | 2011-10-15 | Inst Clayton De La Rech | Verfahren und zusammensetzungen im zusammenhang mit verbesserten lentivirusvektor- produktionssystemen |
| JP2005500061A (ja) | 2001-08-20 | 2005-01-06 | ザ スクリップス リサーチ インスティテュート | Ｃｎｎについての亜鉛フィンガー結合ドメイン |
| US7355012B2 (en) | 2001-09-26 | 2008-04-08 | United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Mutated anti-CD22 antibodies with increased affinity to CD22-expressing leukemia cells |
| RU2305708C2 (ru) | 2001-10-02 | 2007-09-10 | Энститю Клейтон Де Ля Решерш | Рекомбинантный лентивирусный вектор, клетка-хозяин, трансдуцированная лентивирусным вектором, способ ее трансдукции и применение |
| MX359371B (es) | 2001-11-13 | 2018-09-25 | Univ Pennsylvania | Un metodo para detectar y/o identificar secuencias del virus adeno-asociado y aislamiento de secuencias novedosas identificadas de ese modo. |
| US7939059B2 (en) | 2001-12-10 | 2011-05-10 | California Institute Of Technology | Method for the generation of antigen-specific lymphocytes |
| DK2573170T3 (en) | 2001-12-17 | 2018-04-09 | Univ Pennsylvania | Sequences of adeno-associated virus (AAV) serotype 9, vectors containing them, and their use |
| US7262054B2 (en) | 2002-01-22 | 2007-08-28 | Sangamo Biosciences, Inc. | Zinc finger proteins for DNA binding and gene regulation in plants |
| US7361635B2 (en) | 2002-08-29 | 2008-04-22 | Sangamo Biosciences, Inc. | Simultaneous modulation of multiple genes |
| DE60333487D1 (de) | 2002-12-13 | 2010-09-02 | Genetix Pharmaceuticals Inc | Therapeutische retrovirus-vektoren für gentherapie |
| US7888121B2 (en) | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| EP2345731B1 (en) | 2003-09-30 | 2015-10-21 | The Trustees of the University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
| US7982011B2 (en) | 2003-11-25 | 2011-07-19 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Mutated anti-cd22 antibodies and immunoconjugates |
| US7972854B2 (en) | 2004-02-05 | 2011-07-05 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| AU2005232665B2 (en) | 2004-04-08 | 2010-05-13 | Sangamo Therapeutics, Inc. | Methods and compositions for treating neuropathic and neurodegenerative conditions |
| US7253273B2 (en) | 2004-04-08 | 2007-08-07 | Sangamo Biosciences, Inc. | Treatment of neuropathic pain with zinc finger proteins |
| ES2525067T3 (es) | 2005-04-07 | 2014-12-17 | The Trustees Of The University Of Pennsylvania | Método de incremento de la función de un vector de AAV |
| ES2582091T3 (es) | 2005-10-18 | 2016-09-09 | Precision Biosciences | Meganucleasas diseñadas racionalmente con especificidad de secuencia y afinidad de unión a ADN alteradas |
| EP2132322A4 (en) | 2007-03-02 | 2013-02-20 | Richmond Chemical Corp | METHOD FOR INCREASING YIELD AND IMPROVING PURIFICATION OF PRODUCTS FROM REACTIONS WITH TRANSAMINASE |
| DK2185192T3 (en) | 2007-08-03 | 2019-02-18 | Pasteur Institut | LENTIVIRAL TRANSFER VECTORS AND THEIR MEDICAL USES |
| US8586526B2 (en) | 2010-05-17 | 2013-11-19 | Sangamo Biosciences, Inc. | DNA-binding proteins and uses thereof |
| US9089520B2 (en) | 2010-05-21 | 2015-07-28 | Baylor College Of Medicine | Methods for inducing selective apoptosis |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| CA3111953C (en) | 2011-04-05 | 2023-10-24 | Cellectis | Method for the generation of compact tale-nucleases and uses thereof |
| CN103946952A (zh) | 2011-09-16 | 2014-07-23 | 宾夕法尼亚大学董事会 | 用于治疗癌症的rna改造的t细胞 |
| US20140359799A1 (en) | 2011-12-23 | 2014-12-04 | Case Western Reserve University | Targeted gene modification using hybrid recombinant adeno-associated virus |
| WO2013130824A1 (en) | 2012-02-29 | 2013-09-06 | Sangamo Biosciences, Inc. | Methods and compositions for treating huntington's disease |
| RU2766608C2 (ru) | 2012-04-11 | 2022-03-15 | Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретари, Департмент Оф Хелс Энд Хьюман Сёрвисез | Химерные антигенные рецепторы, нацеленные на антиген созревания b-клеток |
| GB201212902D0 (en) | 2012-07-20 | 2012-09-05 | Univ Singapore | Combinatoric encoding methods for microarrays |
| WO2014068079A1 (en) | 2012-11-01 | 2014-05-08 | Max-Delbrück-Centrum für Molekulare Medizin | An antibody that binds cd269 (bcma) suitable for use in the treatment of plasma cell diseases such as multiple myeloma and autoimmune diseases |
| CA2939411A1 (en) | 2014-02-27 | 2015-09-03 | Ucl Business Plc | Ligand |
| KR102526945B1 (ko) | 2014-04-30 | 2023-04-27 | 막스-델부뤽-센트럼 퓌어 몰레쿨라레 메디친 인 데어 헬름홀츠-게마인샤프트 | Ｃｄ269에 대한 인간화 항체 |
| US20160017288A1 (en) * | 2014-05-28 | 2016-01-21 | Eitan Moshe Akirav | Method for inducing the formation of islet structures and improving beta cell function |
| BR112017001183A2 (pt) | 2014-07-21 | 2017-11-28 | Novartis Ag | tratamento de câncer usando receptor de antígeno quimérico anti-bcma humanizado |
| ES2878449T3 (es) | 2014-07-24 | 2021-11-18 | 2Seventy Bio Inc | Receptores antigénicos quiméricos de BCMA |
| EP2990416B1 (en) | 2014-08-29 | 2018-06-20 | GEMoaB Monoclonals GmbH | Universal chimeric antigen receptor expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders |
| WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
| AU2016243583B2 (en) | 2015-03-27 | 2022-03-10 | President And Fellows Of Harvard College | Modified T cells and methods of making and using the same |
| CN107921148A (zh) | 2015-05-08 | 2018-04-17 | 哈佛学院校长同事会 | 通用供体干细胞和相关方法 |
| US20180291080A1 (en) | 2015-09-28 | 2018-10-11 | Trustees Of Dartmouth College | Chimeric antigen receptor, regulatory cells and methods of use |
| JP2018534264A (ja) | 2015-09-28 | 2018-11-22 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 自己免疫および同種免疫への治療的介入としてのキメラ抗原受容体（ｃａｒ）ｔ細胞 |
| CA3025667A1 (en) | 2016-06-08 | 2017-12-14 | Intrexon Corporation | Cd33 specific chimeric antigen receptors |
| JP2020505025A (ja) | 2017-01-13 | 2020-02-20 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 免疫工学的な改変をした多能性細胞 |
| CN110650975B (zh) | 2017-05-15 | 2024-04-05 | 美国卫生和人力服务部 | 双顺反子嵌合抗原受体及其用途 |
| KR102761791B1 (ko) | 2017-06-26 | 2025-02-05 | 더 브로드 인스티튜트, 인코퍼레이티드 | 표적화된 핵산 편집을 위한 crispr/cas-아데닌 데아미나아제 기반 조성물, 시스템 및 방법 |
| WO2019005886A1 (en) | 2017-06-26 | 2019-01-03 | The Broad Institute, Inc. | CRISPR / CAS-CYTIDINE DEAMINASE COMPOSITIONS, SYSTEMS AND METHODS FOR TARGETED EDITING OF NUCLEIC ACIDS |
| US20210079366A1 (en) | 2017-12-22 | 2021-03-18 | The Broad Institute, Inc. | Cas12a systems, methods, and compositions for targeted rna base editing |
| WO2019126709A1 (en) | 2017-12-22 | 2019-06-27 | The Broad Institute, Inc. | Cas12b systems, methods, and compositions for targeted dna base editing |
| EP3728576A4 (en) | 2017-12-22 | 2021-11-24 | The Broad Institute, Inc. | CAS12B SYSTEMS, METHODS AND COMPOSITIONS FOR SPECIFIC EDITING OF RNA BASES |
| CA3109078A1 (en) | 2018-07-17 | 2020-01-23 | The Regents Of The University Of California | Cells differentiated from immunoengineered pluripotent cells |
| WO2020018620A1 (en) | 2018-07-17 | 2020-01-23 | The Regents Of The University Of California | Chimeric antigen receptor t cells derived from immunoengineered pluripotent stem cells |
| WO2020051562A2 (en) | 2018-09-07 | 2020-03-12 | Beam Therapeutics Inc. | Compositions and methods for improving base editing |
| WO2020181195A1 (en) | 2019-03-06 | 2020-09-10 | The Broad Institute, Inc. | T:a to a:t base editing through adenine excision |
| WO2020181193A1 (en) | 2019-03-06 | 2020-09-10 | The Broad Institute, Inc. | T:a to a:t base editing through adenosine methylation |
| WO2020181178A1 (en) | 2019-03-06 | 2020-09-10 | The Broad Institute, Inc. | T:a to a:t base editing through thymine alkylation |
| WO2020181202A1 (en) | 2019-03-06 | 2020-09-10 | The Broad Institute, Inc. | A:t to t:a base editing through adenine deamination and oxidation |
| WO2020191233A1 (en) | 2019-03-19 | 2020-09-24 | The Broad Institute, Inc. | Methods and compositions for editing nucleotide sequences |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| WO2021146222A1 (en) | 2020-01-13 | 2021-07-22 | Sana Biotechnology, Inc. | Modification of blood type antigens |
| EP4100519A2 (en) | 2020-02-05 | 2022-12-14 | The Broad Institute, Inc. | Adenine base editors and uses thereof |
| IL297761A (en) | 2020-05-08 | 2022-12-01 | Broad Inst Inc | Methods and compositions for simultaneously editing two helices of a designated double-helix nucleotide sequence |
| CA3193099A1 (en) | 2020-09-24 | 2022-03-31 | David R. Liu | Prime editing guide rnas, compositions thereof, and methods of using the same |
-
2022
- 2022-08-11 AU AU2022325232A patent/AU2022325232A1/en active Pending
- 2022-08-11 CA CA3227108A patent/CA3227108A1/en active Pending
- 2022-08-11 KR KR1020247007975A patent/KR20240073006A/ko active Pending
- 2022-08-11 WO PCT/US2022/074878 patent/WO2023019229A1/en not_active Ceased
- 2022-08-11 JP JP2024508656A patent/JP2024531234A/ja active Pending
- 2022-08-11 IL IL310691A patent/IL310691A/en unknown
- 2022-08-11 MX MX2024001208A patent/MX2024001208A/es unknown
- 2022-08-11 EP EP22790155.0A patent/EP4384189A1/en active Pending
-
2023
- 2023-08-14 US US18/449,625 patent/US20240010988A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2023019229A1 (en) | 2023-02-16 |
| KR20240073006A (ko) | 2024-05-24 |
| US20240010988A1 (en) | 2024-01-11 |
| IL310691A (en) | 2024-04-01 |
| JP2024531234A (ja) | 2024-08-29 |
| EP4384189A1 (en) | 2024-06-19 |
| MX2024001208A (es) | 2024-04-22 |
| CA3227108A1 (en) | 2023-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11987628B2 (en) | Methods and compositions for modulating CAR-T activity | |
| US20260053851A1 (en) | Inducible systems for altering gene expression in hypoimmunogenic cells | |
| US20240425820A1 (en) | Genetically modified cells for allogeneic cell therapy to reduce complement-mediated inflammatory reactions | |
| US20250127820A1 (en) | Genetically modified cells for allogeneic cell therapy to reduce instant blood mediated inflammatory reactions | |
| US20240226164A1 (en) | Hypoimmunogenic cells comprising engineered hla-e or hla-g | |
| US20240010988A1 (en) | Genetically modified primary cells for allogeneic cell therapy | |
| US20240358761A1 (en) | Genetically modified cells for allogeneic cell therapy | |
| US20240316198A1 (en) | Altered expression of y chromosome-linked antigens in hypoimmunogenic cells | |
| CN118451178A (zh) | 用于同种异体细胞疗法的遗传修饰原代细胞 | |
| CN118382693A (zh) | 降低即刻经血液介导的炎性反应的同种异体细胞疗法的遗传修饰细胞 | |
| CN118401653A (zh) | 用于同种异体细胞疗法的遗传修饰细胞 | |
| CN118434844A (zh) | 用于减少补体介导的炎症反应的同种异体细胞疗法的基因修饰的细胞 | |
| EA049445B1 (ru) | Способы и композиции для модуляции активности car-t-клеток |