CN112105720A - 一种基因工程化的免疫淋巴细胞及其制备方法 - Google Patents
一种基因工程化的免疫淋巴细胞及其制备方法 Download PDFInfo
- Publication number
- CN112105720A CN112105720A CN201980031427.9A CN201980031427A CN112105720A CN 112105720 A CN112105720 A CN 112105720A CN 201980031427 A CN201980031427 A CN 201980031427A CN 112105720 A CN112105720 A CN 112105720A
- Authority
- CN
- China
- Prior art keywords
- cells
- lymphocyte
- cell
- molecule
- engineered
- 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
- 210000004698 lymphocyte Anatomy 0.000 title claims abstract description 90
- 238000002360 preparation method Methods 0.000 title description 11
- 210000004027 cell Anatomy 0.000 claims abstract description 149
- 210000000822 natural killer cell Anatomy 0.000 claims abstract description 55
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 claims abstract description 46
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 claims abstract description 46
- 108091054437 MHC class I family Proteins 0.000 claims abstract description 36
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 21
- 230000022534 cell killing Effects 0.000 claims abstract description 18
- 108010076504 Protein Sorting Signals Proteins 0.000 claims abstract description 12
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- 102000043129 MHC class I family Human genes 0.000 claims abstract description 10
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 claims abstract description 4
- 102100027314 Beta-2-microglobulin Human genes 0.000 claims abstract 3
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 53
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 claims description 52
- 108090000623 proteins and genes Proteins 0.000 claims description 45
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 claims description 32
- 108091033409 CRISPR Proteins 0.000 claims description 30
- 102000004169 proteins and genes Human genes 0.000 claims description 29
- 108091008874 T cell receptors Proteins 0.000 claims description 20
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 20
- 108010042407 Endonucleases Proteins 0.000 claims description 17
- 102000004533 Endonucleases Human genes 0.000 claims description 17
- 238000012217 deletion Methods 0.000 claims description 14
- 230000037430 deletion Effects 0.000 claims description 14
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 11
- 238000005520 cutting process Methods 0.000 claims description 10
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 9
- 102000007079 Peptide Fragments Human genes 0.000 claims description 8
- 108010033276 Peptide Fragments Proteins 0.000 claims description 8
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 8
- 230000007018 DNA scission Effects 0.000 claims description 6
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
- 239000012634 fragment Substances 0.000 claims description 5
- 230000002779 inactivation Effects 0.000 claims description 5
- 150000007523 nucleic acids Chemical group 0.000 claims description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 4
- 101150076800 B2M gene Proteins 0.000 claims description 4
- 210000002540 macrophage Anatomy 0.000 claims description 3
- 108010052875 Adenine deaminase Proteins 0.000 claims description 2
- 101710117995 B-lymphocyte antigen CD19 Proteins 0.000 claims description 2
- 108010080611 Cytosine Deaminase Proteins 0.000 claims description 2
- 102000000311 Cytosine Deaminase Human genes 0.000 claims description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 2
- 101150000578 HLA-B gene Proteins 0.000 claims description 2
- 101150035071 HLA-C gene Proteins 0.000 claims description 2
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 2
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 50
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 41
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 41
- 230000002147 killing effect Effects 0.000 description 25
- 230000000735 allogeneic effect Effects 0.000 description 21
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 18
- 238000010362 genome editing Methods 0.000 description 15
- 210000004986 primary T-cell Anatomy 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 238000001890 transfection Methods 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- 101710163270 Nuclease Proteins 0.000 description 8
- 108091027544 Subgenomic mRNA Proteins 0.000 description 8
- 241000713666 Lentivirus Species 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 210000000170 cell membrane Anatomy 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 108091008042 inhibitory receptors Proteins 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 230000006044 T cell activation Effects 0.000 description 6
- 230000003213 activating effect Effects 0.000 description 6
- 101150063416 add gene Proteins 0.000 description 6
- 125000003275 alpha amino acid group Chemical group 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 230000004807 localization Effects 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 4
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 4
- 108010024164 HLA-G Antigens Proteins 0.000 description 4
- 239000012124 Opti-MEM Substances 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 239000000306 component Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 102000006306 Antigen Receptors Human genes 0.000 description 3
- 108010083359 Antigen Receptors Proteins 0.000 description 3
- 238000010453 CRISPR/Cas method Methods 0.000 description 3
- 108010075704 HLA-A Antigens Proteins 0.000 description 3
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 description 3
- 101150069255 KLRC1 gene Proteins 0.000 description 3
- 101100404845 Macaca mulatta NKG2A gene Proteins 0.000 description 3
- 102100022682 NKG2-A/NKG2-B type II integral membrane protein Human genes 0.000 description 3
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 241000194020 Streptococcus thermophilus Species 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102100028966 HLA class I histocompatibility antigen, alpha chain F Human genes 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000986080 Homo sapiens HLA class I histocompatibility antigen, alpha chain F Proteins 0.000 description 2
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 2
- 241000186805 Listeria innocua Species 0.000 description 2
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 2
- 230000006051 NK cell activation Effects 0.000 description 2
- 241000588650 Neisseria meningitidis Species 0.000 description 2
- 101710153660 Nuclear receptor corepressor 2 Proteins 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 108091028113 Trans-activating crRNA Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 101150100265 cif-1 gene Proteins 0.000 description 2
- 238000011198 co-culture assay Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 108010026638 endodeoxyribonuclease FokI Proteins 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 238000003197 gene knockdown Methods 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000001778 pluripotent stem cell Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000003151 transfection method Methods 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- RXACEEPNTRHYBQ-UHFFFAOYSA-N 2-[[2-[[2-[(2-sulfanylacetyl)amino]acetyl]amino]acetyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)CNC(=O)CNC(=O)CS RXACEEPNTRHYBQ-UHFFFAOYSA-N 0.000 description 1
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 1
- 101150033839 4 gene Proteins 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 101001005269 Arabidopsis thaliana Ceramide synthase 1 LOH3 Proteins 0.000 description 1
- 101001005312 Arabidopsis thaliana Ceramide synthase LOH1 Proteins 0.000 description 1
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- -1 C-Met Proteins 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102100028801 Calsyntenin-1 Human genes 0.000 description 1
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101100438439 Escherichia coli (strain K12) ygbT gene Proteins 0.000 description 1
- 101150106478 GPS1 gene Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102100032530 Glypican-3 Human genes 0.000 description 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 1
- 101150118346 HLA-A gene Proteins 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 108010058607 HLA-B Antigens Proteins 0.000 description 1
- 108010021736 HLA-B15 Antigen Proteins 0.000 description 1
- 108010091938 HLA-B7 Antigen Proteins 0.000 description 1
- 108010052199 HLA-C Antigens Proteins 0.000 description 1
- 108010070768 HLA-C*03 antigen Proteins 0.000 description 1
- 108010007655 HLA-C*70 antigen Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 description 1
- 101001014668 Homo sapiens Glypican-3 Proteins 0.000 description 1
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 1
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 1
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 1
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 1
- 102000002698 KIR Receptors Human genes 0.000 description 1
- 108010043610 KIR Receptors Proteins 0.000 description 1
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 108091008043 NK cell inhibitory receptors Proteins 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- 101150030723 RIR2 gene Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 101800000684 Ribonuclease H Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101000668858 Spinacia oleracea 30S ribosomal protein S1, chloroplastic Proteins 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 101100166147 Streptococcus thermophilus cas9 gene Proteins 0.000 description 1
- 101000898746 Streptomyces clavuligerus Clavaminate synthase 1 Proteins 0.000 description 1
- 102100035721 Syndecan-1 Human genes 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 238000010459 TALEN Methods 0.000 description 1
- 101100329497 Thermoproteus tenax (strain ATCC 35583 / DSM 2078 / JCM 9277 / NBRC 100435 / Kra 1) cas2 gene Proteins 0.000 description 1
- 241001313536 Thermothelomyces thermophila Species 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 1
- 102100037116 Transcription elongation factor 1 homolog Human genes 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 101150100826 UL40 gene Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 101710185494 Zinc finger protein Proteins 0.000 description 1
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 101150058049 car gene Proteins 0.000 description 1
- 101150000705 cas1 gene Proteins 0.000 description 1
- 101150038500 cas9 gene Proteins 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000006690 co-activation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000008358 core component Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 108010087914 epidermal growth factor receptor VIII Proteins 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 102000047279 human B2M Human genes 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000011502 immune monitoring Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005316 response function Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4613—Natural-killer cells [NK or NK-T]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4632—T-cell receptors [TCR]; antibody T-cell receptor constructs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464411—Immunoglobulin superfamily
- A61K39/464412—CD19 or B4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
-
- 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
- C12N15/62—DNA sequences coding for fusion 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Oncology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
提供了一种改造的淋巴细胞，细胞表面缺失I类MHC分子并表达包含信号肽、呈递肽段、B2M蛋白、HLA‑E重链和连接序列的嵌合多聚体单链分子。还提供了改造的淋巴细胞的制备方法和在抑制NK细胞杀伤中的用途。
Description
PCT国内申请，说明书已公开。
Claims (30)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2018105953469 | 2018-06-11 | ||
| CN201810595346 | 2018-06-11 | ||
| PCT/CN2019/090604 WO2019238015A1 (zh) | 2018-06-11 | 2019-06-10 | 一种基因工程化的免疫淋巴细胞及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112105720A true CN112105720A (zh) | 2020-12-18 |
Family
ID=68842697
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980031427.9A Pending CN112105720A (zh) | 2018-06-11 | 2019-06-10 | 一种基因工程化的免疫淋巴细胞及其制备方法 |
| CN201980031497.4A Pending CN112105650A (zh) | 2018-06-11 | 2019-06-10 | 一种嵌合单链分子及其应用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980031497.4A Pending CN112105650A (zh) | 2018-06-11 | 2019-06-10 | 一种嵌合单链分子及其应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN112105720A (zh) |
| WO (2) | WO2019238016A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112830973B (zh) * | 2020-04-08 | 2022-11-01 | 苏州克睿基因生物科技有限公司 | 嵌合多肽及其用途 |
| CN117940465A (zh) * | 2021-08-12 | 2024-04-26 | 苏州克睿基因生物科技有限公司 | 经修饰的细胞、其制备方法及应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107723275A (zh) * | 2017-10-20 | 2018-02-23 | 重庆精准生物技术有限公司 | 通用型car‑t细胞及其制备方法和应用 |
| WO2018064594A2 (en) * | 2016-09-29 | 2018-04-05 | Nantkwest, Inc. | Hla class i-deficient nk-92 cells with decreased immunogenicity |
-
2019
- 2019-06-10 CN CN201980031427.9A patent/CN112105720A/zh active Pending
- 2019-06-10 WO PCT/CN2019/090605 patent/WO2019238016A1/zh active Application Filing
- 2019-06-10 WO PCT/CN2019/090604 patent/WO2019238015A1/zh active Application Filing
- 2019-06-10 CN CN201980031497.4A patent/CN112105650A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018064594A2 (en) * | 2016-09-29 | 2018-04-05 | Nantkwest, Inc. | Hla class i-deficient nk-92 cells with decreased immunogenicity |
| CN107723275A (zh) * | 2017-10-20 | 2018-02-23 | 重庆精准生物技术有限公司 | 通用型car‑t细胞及其制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019238016A1 (zh) | 2019-12-19 |
| WO2019238015A1 (zh) | 2019-12-19 |
| CN112105650A (zh) | 2020-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108601821B (zh) | 包含经修饰的人T细胞受体α恒定区基因的经遗传修饰的细胞 | |
| JP6681837B2 (ja) | 同種移植に適合するｔ細胞を作製するための方法 | |
| JP6846429B2 (ja) | ヒトβ−２ミクログロブリン遺伝子に見られる認識配列を有する操作されたメガヌクレアーゼ | |
| AU2014339926B2 (en) | Polyclonal gamma delta T cells for immunotherapy | |
| US20190161530A1 (en) | Chimeric antigen receptor t cell compositions | |
| JP7190096B2 (ja) | 遺伝子編集ｔ細胞及びその使用 | |
| JP2021506243A (ja) | Ｔ細胞受容体及びβ２ミクログロブリン発現を排除するように遺伝子改変された不死化ＣＡＲ−Ｔ細胞 | |
| KR20210148293A (ko) | 마이크로RNA-적응 shRNA(shRNAmiR)를 포함하는 유전자-변형 면역 세포 | |
| KR102617818B1 (ko) | 인간 t 세포 수용체 알파 불변 영역 유전자에 대한 특이성을 갖는 최적화된 조작된 뉴클레아제 | |
| WO2019005957A1 (en) | GENETICALLY MODIFIED T CELLS COMPRISING A MODIFIED INTRON IN THE ALPHA T CELL RECEPTOR GENE | |
| CN116425882A (zh) | 嵌合蛋白 | |
| CN108531457A (zh) | 一种Cas9/RNP敲除T细胞PD-1和LAG3基因及制备CAR-T细胞的方法 | |
| CN109678965A (zh) | 嵌合抗原受体及其基因和重组表达载体、cd22-cd19双靶向性的t细胞及其应用 | |
| JP7235391B2 (ja) | 人工的に操作された免疫細胞 | |
| Tal et al. | An NCR1-based chimeric receptor endows T-cells with multiple anti-tumor specificities | |
| CN112105720A (zh) | 一种基因工程化的免疫淋巴细胞及其制备方法 | |
| CN111875708B (zh) | 一种嵌合抗原受体t淋巴细胞及其在制备治疗实体肿瘤的产品中的应用 | |
| CN115948344A (zh) | 嵌合抗原受体nk细胞、制备方法及其用途 | |
| US20230133564A1 (en) | Cd3-fusion protein and uses thereof | |
| US20220411479A1 (en) | Cd20 chimeric antigen receptors and methods of use for immunotherapy | |
| WO2024047561A1 (en) | Biomaterials and processes for immune synapse modulation of hypoimmunogenicity | |
| CN114929867A (zh) | 一种经修饰的免疫效应细胞及其用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20201218 |
|
| WD01 | Invention patent application deemed withdrawn after publication |