WO2022129472A1 - Safe immuno-stealth cells - Google Patents
Safe immuno-stealth cells Download PDFInfo
- Publication number
- WO2022129472A1 WO2022129472A1 PCT/EP2021/086399 EP2021086399W WO2022129472A1 WO 2022129472 A1 WO2022129472 A1 WO 2022129472A1 EP 2021086399 W EP2021086399 W EP 2021086399W WO 2022129472 A1 WO2022129472 A1 WO 2022129472A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cell
- hla
- gene
- genes
- hsv
- Prior art date
Links
- 210000004027 cell Anatomy 0.000 claims description 382
- 108090000623 proteins and genes Proteins 0.000 claims description 375
- 210000004962 mammalian cell Anatomy 0.000 claims description 234
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 claims description 164
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 claims description 156
- 238000000034 method Methods 0.000 claims description 105
- 101100382122 Homo sapiens CIITA gene Proteins 0.000 claims description 69
- 230000002950 deficient Effects 0.000 claims description 50
- 108700002010 MHC class II transactivator Proteins 0.000 claims description 47
- 230000004927 fusion Effects 0.000 claims description 45
- 102100026371 MHC class II transactivator Human genes 0.000 claims description 40
- 210000000130 stem cell Anatomy 0.000 claims description 37
- 108700028369 Alleles Proteins 0.000 claims description 26
- 210000000349 chromosome Anatomy 0.000 claims description 24
- 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 14
- 210000000822 natural killer cell Anatomy 0.000 claims description 14
- 102100028096 Homeobox protein Nkx-6.2 Human genes 0.000 claims description 13
- 101000578254 Homo sapiens Homeobox protein Nkx-6.1 Proteins 0.000 claims description 13
- 101000578258 Homo sapiens Homeobox protein Nkx-6.2 Proteins 0.000 claims description 13
- 208000017667 Chronic Disease Diseases 0.000 claims description 12
- 210000003890 endocrine cell Anatomy 0.000 claims description 12
- 230000000415 inactivating effect Effects 0.000 claims description 12
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 11
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims description 10
- 238000000338 in vitro Methods 0.000 claims description 10
- 210000001519 tissue Anatomy 0.000 claims description 10
- 101100518002 Danio rerio nkx2.2a gene Proteins 0.000 claims description 9
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 claims description 9
- 102100027886 Homeobox protein Nkx-2.2 Human genes 0.000 claims description 9
- 101100460496 Homo sapiens NKX2-2 gene Proteins 0.000 claims description 9
- 101000603702 Homo sapiens Neurogenin-3 Proteins 0.000 claims description 9
- 102100038553 Neurogenin-3 Human genes 0.000 claims description 9
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 9
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 9
- 210000001808 exosome Anatomy 0.000 claims description 9
- 210000002569 neuron Anatomy 0.000 claims description 9
- 230000002207 retinal effect Effects 0.000 claims description 9
- 210000003583 retinal pigment epithelium Anatomy 0.000 claims description 9
- 206010016654 Fibrosis Diseases 0.000 claims description 8
- 208000030090 Acute Disease Diseases 0.000 claims description 7
- 102000004877 Insulin Human genes 0.000 claims description 7
- 102100023915 Insulin Human genes 0.000 claims description 7
- 108090001061 Insulin Proteins 0.000 claims description 7
- 229940125396 insulin Drugs 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 6
- 210000001130 astrocyte Anatomy 0.000 claims description 6
- 210000004443 dendritic cell Anatomy 0.000 claims description 6
- 210000004002 dopaminergic cell Anatomy 0.000 claims description 6
- 210000003027 ear inner Anatomy 0.000 claims description 6
- 230000002124 endocrine Effects 0.000 claims description 6
- 210000002950 fibroblast Anatomy 0.000 claims description 6
- 210000002768 hair cell Anatomy 0.000 claims description 6
- 210000003494 hepatocyte Anatomy 0.000 claims description 6
- 210000002865 immune cell Anatomy 0.000 claims description 6
- 210000001153 interneuron Anatomy 0.000 claims description 6
- 230000000968 intestinal effect Effects 0.000 claims description 6
- 210000002510 keratinocyte Anatomy 0.000 claims description 6
- 210000003734 kidney Anatomy 0.000 claims description 6
- 210000002540 macrophage Anatomy 0.000 claims description 6
- 210000003061 neural cell Anatomy 0.000 claims description 6
- 210000004248 oligodendroglia Anatomy 0.000 claims description 6
- 210000002220 organoid Anatomy 0.000 claims description 6
- 230000009996 pancreatic endocrine effect Effects 0.000 claims description 6
- 210000004500 stellate cell Anatomy 0.000 claims description 6
- 230000001054 cortical effect Effects 0.000 claims description 5
- 210000005155 neural progenitor cell Anatomy 0.000 claims description 5
- VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 claims description 4
- 201000004569 Blindness Diseases 0.000 claims description 4
- 108010075254 C-Peptide Proteins 0.000 claims description 4
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 4
- 206010011878 Deafness Diseases 0.000 claims description 4
- 208000008069 Geographic Atrophy Diseases 0.000 claims description 4
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 230000004761 fibrosis Effects 0.000 claims description 4
- 230000010370 hearing loss Effects 0.000 claims description 4
- 231100000888 hearing loss Toxicity 0.000 claims description 4
- 208000016354 hearing loss disease Diseases 0.000 claims description 4
- 208000019622 heart disease Diseases 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
- 208000032376 Lung infection Diseases 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 102100027314 Beta-2-microglobulin Human genes 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 325
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 293
- 108010078473 HLA-E antigen Proteins 0.000 description 77
- 102000004169 proteins and genes Human genes 0.000 description 60
- 229960002963 ganciclovir Drugs 0.000 description 44
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 42
- 108090000765 processed proteins & peptides Proteins 0.000 description 35
- 101150076800 B2M gene Proteins 0.000 description 29
- 108010076504 Protein Sorting Signals Proteins 0.000 description 28
- 108020004440 Thymidine kinase Proteins 0.000 description 28
- 230000014509 gene expression Effects 0.000 description 26
- 108020001507 fusion proteins Proteins 0.000 description 25
- 102000037865 fusion proteins Human genes 0.000 description 25
- 101150074628 HLA-E gene Proteins 0.000 description 24
- 210000001671 embryonic stem cell Anatomy 0.000 description 19
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 description 18
- 102000006601 Thymidine Kinase Human genes 0.000 description 18
- 150000001413 amino acids Chemical group 0.000 description 17
- 238000010459 TALEN Methods 0.000 description 16
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 16
- 230000004069 differentiation Effects 0.000 description 16
- 108020004999 messenger RNA Proteins 0.000 description 13
- 210000001778 pluripotent stem cell Anatomy 0.000 description 13
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 12
- 108010075704 HLA-A Antigens Proteins 0.000 description 12
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 description 12
- 150000007523 nucleic acids Chemical group 0.000 description 12
- 210000005260 human cell Anatomy 0.000 description 11
- 102100034229 Citramalyl-CoA lyase, mitochondrial Human genes 0.000 description 10
- 101000710917 Homo sapiens Citramalyl-CoA lyase, mitochondrial Proteins 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 230000030833 cell death Effects 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 230000002779 inactivation Effects 0.000 description 8
- 238000003780 insertion Methods 0.000 description 8
- 230000037431 insertion Effects 0.000 description 8
- 230000010354 integration Effects 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 238000012239 gene modification Methods 0.000 description 7
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 7
- 206010010144 Completed suicide Diseases 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000037451 immune surveillance Effects 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 5
- 108010024164 HLA-G Antigens Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 208000036142 Viral infection Diseases 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 230000024245 cell differentiation Effects 0.000 description 5
- 230000005017 genetic modification Effects 0.000 description 5
- 235000013617 genetically modified food Nutrition 0.000 description 5
- 210000003917 human chromosome Anatomy 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 101150055030 Clybl gene Proteins 0.000 description 4
- 108010051219 Cre recombinase Proteins 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 210000001178 neural stem cell Anatomy 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 3
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 3
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 3
- 108010058607 HLA-B Antigens Proteins 0.000 description 3
- 108010052199 HLA-C Antigens Proteins 0.000 description 3
- 102100032063 Neurogenic differentiation factor 1 Human genes 0.000 description 3
- 108050000588 Neurogenic differentiation factor 1 Proteins 0.000 description 3
- 241000700584 Simplexvirus Species 0.000 description 3
- 101150003725 TK gene Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000010362 genome editing Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 208000023516 stroke disease Diseases 0.000 description 3
- 230000003614 tolerogenic effect Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 2
- 108091033409 CRISPR Proteins 0.000 description 2
- 238000010354 CRISPR gene editing Methods 0.000 description 2
- 101000691214 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 50S ribosomal protein L44e Proteins 0.000 description 2
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000001109 blastomere Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000032459 dedifferentiation Effects 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 229910052754 neon Inorganic materials 0.000 description 2
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 101100117362 Drosophila melanogaster Doa gene Proteins 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102100028966 HLA class I histocompatibility antigen, alpha chain F Human genes 0.000 description 1
- 102100031546 HLA class II histocompatibility antigen, DO beta chain Human genes 0.000 description 1
- 108010010378 HLA-DP Antigens Proteins 0.000 description 1
- 102000015789 HLA-DP Antigens Human genes 0.000 description 1
- 108010062347 HLA-DQ Antigens Proteins 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 101000986080 Homo sapiens HLA class I histocompatibility antigen, alpha chain F Proteins 0.000 description 1
- 101000866281 Homo sapiens HLA class II histocompatibility antigen, DO beta chain Proteins 0.000 description 1
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 1
- 101000983747 Homo sapiens MHC class II transactivator Proteins 0.000 description 1
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
- 101000579126 Mus musculus Phosphoglycerate kinase 1 Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 235000011449 Rosa Nutrition 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 210000001840 diploid cell Anatomy 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 210000001368 germline stem cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 229940028444 muse Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 230000031942 natural killer cell mediated cytotoxicity Effects 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 210000005132 reproductive cell Anatomy 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000005758 transcription activity Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000002444 unipotent stem cell Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
Classifications
-
- 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
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
-
- 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
-
- 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
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem 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
- C12N2510/00—Genetically modified cells
Definitions
- B2M/HLA-E fusion gene such as a B2M/HLA-E*0101 gene and/or a B2M/HLA-E*0103 gene, into said mammalian cell
- the expression "at distinct locations” as used herein means "at different loci on the genome”.
- the expression refers for example to more than one nucleic acid sequence insertion, where said 2 or more nucleic acid sequences are not inserted on the same locus on the genome, i.e. on the one same position on the genome. Rather, said 2 or more nucleic acid sequences are inserted at different loci on the genome. For example, if inserted on the same chromosome, the 2 or more sequences are separated from each other by a number of nucleotides after insertion.
- the expression "distinct locations” may include the same locus located on 2 chromosomes of a pair of chromosomes.
- HLA-II deficient cell means a cell which comprises no HLA-II protein on its cell surface.
- the absence of HLA-II proteins on the cell surface may result from the absence of any expressible HLA-II gene in the cell, e.g. due to inactivation of all HLA-II genes.
- the absence of HLA-II proteins on the cell surface may result from the cell being CIITA deficient.
- HSV-TK gene and TK-sr39 :
- the present invention provides a mammalian cell which has knock-ins of both B2M/HLA-E*0101 and B2M/HLA-E*0103 genes into an otherwise B2M deficient cell.
- Said differentiated cell may be derived from a stem cell, a pluripotential cell or an iPS cell of the invention according to one of the differentiation methods described in the publications referred to in the below list:
- a clone containing four HSV-TK copies from the protocol above is electroporated with a total of 200ng TALEN® mRNA pair (ThermoFisher®, forward target sequence: TCTCGCTCCGTGGCCTT (SEQ ID NO 15), reverse target sequence: AGCCTCCAGGCCAGAAAG (SEQ ID NO 16)) against B2M and 200ng donor plasmid containing 300bp homology arms flanking the TALEN® cut site in B2M, a B2M- HLAIE0101 fusion cassette followed by a mCherry selection cassette and 200ng donor plasmid containing 300bp homology arms flanking the TALEN® cut site in B2M, a B2M-HLAIE0103 fusion cassette followed by a eGFP selection cassette.
- TALEN® mRNA pair ThermoFisher®, forward target sequence: TCTCGCTCCGTGGCCTT (SEQ ID NO 15), reverse target sequence: AGCCTCCAGGCCAGAAAG
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Developmental Biology & Embryology (AREA)
- Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Reproductive Health (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Gynecology & Obstetrics (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP20215272 | 2020-12-18 | ||
EP20215272.4 | 2020-12-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022129472A1 true WO2022129472A1 (en) | 2022-06-23 |
Family
ID=73855659
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2021/086399 WO2022129472A1 (en) | 2020-12-18 | 2021-12-17 | Safe immuno-stealth cells |
Country Status (3)
Country | Link |
---|---|
AR (1) | AR124419A1 (zh) |
TW (1) | TW202242095A (zh) |
WO (1) | WO2022129472A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024008979A1 (en) | 2022-09-30 | 2024-01-11 | Novo Nordisk A/S | A sirp-alpha binding chimeric protein |
Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003046141A2 (en) | 2001-11-26 | 2003-06-05 | Advanced Cell Technology, Inc. | Methods for making and using reprogrammed human somatic cell nuclei and autologous and isogenic human stem cells |
WO2003055992A2 (en) | 2001-12-28 | 2003-07-10 | Cellartis Ab | A method for the establishment of a pluripotent human blastocyst-derived stem cell line |
US20040225112A1 (en) | 2003-05-06 | 2004-11-11 | Crew Mark D. | Genes encoding single chain human leukocyte antigen E (HLA-E) proteins to prevent natural killer cell-mediated cytotoxicity |
WO2007042225A2 (en) | 2005-10-07 | 2007-04-19 | Cellartis Ab | A method for obtaining a xeno-free hbs cell line |
WO2012145384A1 (en) | 2011-04-20 | 2012-10-26 | University Of Washington Through Its Center For Commercialization | Beta-2 microglobulin-deficient cells |
US8586358B2 (en) | 2007-03-09 | 2013-11-19 | University Of Washington | HLA homozygous cells |
WO2015028614A1 (en) | 2013-08-30 | 2015-03-05 | Novo Nordisk A/S | Generation of endocrine progenitor cells from human pluripotent stem cells using small molecules |
WO2017079673A1 (en) * | 2015-11-04 | 2017-05-11 | Fate Therapeutics, Inc. | Genomic engineering of pluripotent cells |
WO2017144695A1 (en) | 2016-02-24 | 2017-08-31 | Novo Nordisk A/S | Generation of functional beta cells from human pluripotent stem cell-derived endocrine progenitors |
WO2018005556A1 (en) | 2016-06-27 | 2018-01-04 | Juno Therapeutics, Inc. | Mhc-e restricted epitopes, binding molecules and related methods and uses |
WO2019032675A1 (en) | 2017-08-08 | 2019-02-14 | Sangamo Therapeutics, Inc. | CELL TARGETING MEDIATED BY A CHIMERIC ANTIGEN RECEPTOR |
WO2019241400A1 (en) * | 2018-06-12 | 2019-12-19 | The Regents Of The University Of California | Stem cell-engineered inkt cell-based off -the-shelf cellular therapy |
WO2020012033A1 (en) * | 2018-07-13 | 2020-01-16 | Lothar Germeroth | Non-immunogenic engineered tissue and methods of producing and using the same |
WO2020072390A1 (en) * | 2018-10-01 | 2020-04-09 | Caribou Biosciences, Inc. | Suicide module compositions and methods |
-
2021
- 2021-12-17 WO PCT/EP2021/086399 patent/WO2022129472A1/en active Application Filing
- 2021-12-17 TW TW110147425A patent/TW202242095A/zh unknown
- 2021-12-17 AR ARP210103566A patent/AR124419A1/es unknown
Patent Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003046141A2 (en) | 2001-11-26 | 2003-06-05 | Advanced Cell Technology, Inc. | Methods for making and using reprogrammed human somatic cell nuclei and autologous and isogenic human stem cells |
WO2003055992A2 (en) | 2001-12-28 | 2003-07-10 | Cellartis Ab | A method for the establishment of a pluripotent human blastocyst-derived stem cell line |
US20040225112A1 (en) | 2003-05-06 | 2004-11-11 | Crew Mark D. | Genes encoding single chain human leukocyte antigen E (HLA-E) proteins to prevent natural killer cell-mediated cytotoxicity |
WO2007042225A2 (en) | 2005-10-07 | 2007-04-19 | Cellartis Ab | A method for obtaining a xeno-free hbs cell line |
US8586358B2 (en) | 2007-03-09 | 2013-11-19 | University Of Washington | HLA homozygous cells |
WO2012145384A1 (en) | 2011-04-20 | 2012-10-26 | University Of Washington Through Its Center For Commercialization | Beta-2 microglobulin-deficient cells |
WO2015028614A1 (en) | 2013-08-30 | 2015-03-05 | Novo Nordisk A/S | Generation of endocrine progenitor cells from human pluripotent stem cells using small molecules |
WO2017079673A1 (en) * | 2015-11-04 | 2017-05-11 | Fate Therapeutics, Inc. | Genomic engineering of pluripotent cells |
WO2017144695A1 (en) | 2016-02-24 | 2017-08-31 | Novo Nordisk A/S | Generation of functional beta cells from human pluripotent stem cell-derived endocrine progenitors |
WO2018005556A1 (en) | 2016-06-27 | 2018-01-04 | Juno Therapeutics, Inc. | Mhc-e restricted epitopes, binding molecules and related methods and uses |
WO2019032675A1 (en) | 2017-08-08 | 2019-02-14 | Sangamo Therapeutics, Inc. | CELL TARGETING MEDIATED BY A CHIMERIC ANTIGEN RECEPTOR |
WO2019241400A1 (en) * | 2018-06-12 | 2019-12-19 | The Regents Of The University Of California | Stem cell-engineered inkt cell-based off -the-shelf cellular therapy |
WO2020012033A1 (en) * | 2018-07-13 | 2020-01-16 | Lothar Germeroth | Non-immunogenic engineered tissue and methods of producing and using the same |
WO2020072390A1 (en) * | 2018-10-01 | 2020-04-09 | Caribou Biosciences, Inc. | Suicide module compositions and methods |
Non-Patent Citations (27)
Title |
---|
ACKERMANN M. ET AL., NAT COMMUN., vol. 9, no. 1, 30 November 2018 (2018-11-30), pages 5088 |
AKTINSON-DELL R. ET AL., ADV EXP MED BIOL., vol. 1175, 2019, pages 383 - 405 |
BEN M'BAREK K ET AL., BIOMATERIALS, 6 November 2019 (2019-11-06), pages 119603 |
BLACK ET AL., CANCER RESEARCH, vol. 61, 1 April 2001 (2001-04-01), pages 3022 - 3026 |
CANDELARIO K.M ET AL., J COMP NEUROL., 19 November 2019 (2019-11-19) |
CHEN B, STEM CELL RES THER., vol. 10, no. 1, 21 May 2019 (2019-05-21), pages 142 |
CHEN KH, AM J TRANSL RES., vol. 11, no. 9, 15 September 2019 (2019-09-15), pages 6232 - 6248 |
COLL M., CELL STEM CELL, vol. 23, no. 1, 5 July 2018 (2018-07-05), pages 101 - 113 |
DEUSE ET AL., NATURE BIOTECHNOLOGY, 2019 |
DOUGHERTY J.A. ET AL., FRONT PHYSIOL, vol. 9, 14 December 2018 (2018-12-14), pages 1794 |
GOOD ML. ET AL., J VIS EXP., no. 152, 24 October 2019 (2019-10-24) |
GORNALUSSE G. ET AL., NATURE BIOTECHNOLOGY, 2017 |
HUANG CY ET AL., J MOL CELL CARDIOL., vol. 138, 23 October 2019 (2019-10-23), pages 1 - 11 |
JEONG M. ET AL., CELL DEATH DIS., vol. 9, no. 9, 11 September 2018 (2018-09-11), pages 922 |
KIRKEBY A. ET AL., CELL REP., vol. 1, no. 6, 28 June 2012 (2012-06-28), pages 703 - 14 |
KITADANI J. ET AL., SCI REP., vol. 8, no. 1, 15 March 2018 (2018-03-15), pages 4569 |
LEES EA ET AL., J VIS EXP., 12 May 2019 (2019-05-12), pages 147 |
LI Z. ET AL., CELL DEATH DIS, vol. 10, no. 10, 10 October 2019 (2019-10-10), pages 763 |
MIYAKE T, INT J RADIAT ONCOL BIOL PHYS., vol. 105, no. 1, 1 September 2019 (2019-09-01), pages 193 - 205 |
NEGORO R. ET AL., STEM CELL REPORTS, vol. 11, no. 6, 11 December 2018 (2018-12-11), pages 1539 - 1550 |
NI P. ET AL., MOL THER METHODS CLIN DEV., vol. 13, 8 April 2019 (2019-04-08), pages 414 - 430 |
NOLBRANT S. ET AL., NAT. PROTOC., no. 9, 12 September 2017 (2017-09-12), pages 1962 - 1979 |
SUN X. ET AL., FRONT CELL NEUROSCI., vol. 13, 3 September 2019 (2019-09-03), pages 394 |
VANSLAMBROUCK JM ET AL., J AM SOC NEPHROL., no. 10, 30 October 2019 (2019-10-30), pages 1811 - 1823 |
YANG R. ET AL., FRONT IMMUNOL., vol. 10, 16 October 2019 (2019-10-16), pages 2346 |
YOUNG ET AL., CANCER GEN. THERAPY, vol. 7, 2000, pages 240 - 246 |
ZHU H. ET AL., METHODS MOL BIOL., vol. 2048, 2019, pages 107 - 119 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024008979A1 (en) | 2022-09-30 | 2024-01-11 | Novo Nordisk A/S | A sirp-alpha binding chimeric protein |
Also Published As
Publication number | Publication date |
---|---|
TW202242095A (zh) | 2022-11-01 |
AR124419A1 (es) | 2023-03-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20210024884A1 (en) | Safe immuno-stealth cells | |
US20220104467A1 (en) | Genetically modified cells, tissues, and organs for treating disease | |
CA3034101A1 (en) | Genome editing enhancers | |
JP2021534806A (ja) | ユニバーサルドナー細胞 | |
US20230272429A1 (en) | Modification of blood type antigens | |
JP2005521403A (ja) | 寛容原性抗原提示細胞 | |
US20230235280A1 (en) | Modified stem cells and methods of use thereof | |
WO2016112779A1 (en) | Modified cells evoking reduced immunogenic responses | |
WO2022129472A1 (en) | Safe immuno-stealth cells | |
WO2022136215A1 (en) | Safe immuno-stealth cells | |
Fairchild et al. | Embryonic stem cells: protecting pluripotency from alloreactivity | |
US11708561B2 (en) | Protection of beta cells from immune attack | |
WO2022191216A1 (ja) | 低免疫原性網膜色素上皮細胞の製造方法 | |
US20240189355A1 (en) | Hypoimmunogenic cells having targeted modifications in mhc class-i genes and methods of use | |
US20230272431A1 (en) | Methods and compositions for editing the b2m locus in b cells | |
EP4219707A1 (en) | Method for producing effector cell having desired specificity | |
WO2023173123A1 (en) | Genetically modified cells and compositions and uses thereof | |
Crane et al. | Living donor organ transplantation—gene therapy | |
US20210238535A1 (en) | Automated production of car-expressing cells | |
KR20230170442A (ko) | 내인성 항원 제시 기전을 이용한 저면역원성 줄기세포 및 이의 제조 방법 | |
KR20230131816A (ko) | 저면역원성 줄기세포, 줄기세포로부터 분화되거나 유래된 저면역원성 세포및 이의 제조방법 | |
WO2024107742A1 (en) | Hypoimmunogenic cells having targeted modifications in mhc class-i genes and methods of use | |
CN118076362A (zh) | 用于改变低免疫原性细胞中的基因表达的诱导型系统 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21831058 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21831058 Country of ref document: EP Kind code of ref document: A1 |