KR102313053B1 - 키메라 주요 조직적합성 복합체(ｍｈｃ) 제ｉ 부류 분자를 발현하는 유전자전이 마우스 - Google Patents
키메라 주요 조직적합성 복합체(ｍｈｃ) 제ｉ 부류 분자를 발현하는 유전자전이 마우스 Download PDFInfo
- Publication number
- KR102313053B1 KR102313053B1 KR1020157028380A KR20157028380A KR102313053B1 KR 102313053 B1 KR102313053 B1 KR 102313053B1 KR 1020157028380 A KR1020157028380 A KR 1020157028380A KR 20157028380 A KR20157028380 A KR 20157028380A KR 102313053 B1 KR102313053 B1 KR 102313053B1
- Authority
- KR
- South Korea
- Prior art keywords
- human
- mouse
- polypeptide
- mhc
- 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.)
- Active
Links
- 108700018351 Major Histocompatibility Complex Proteins 0.000 title description 474
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 title description 469
- 241000699660 Mus musculus Species 0.000 title description 9
- 238000011830 transgenic mouse model Methods 0.000 title description 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 589
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 544
- 229920001184 polypeptide Polymers 0.000 claims abstract description 522
- 108010081355 beta 2-Microglobulin Proteins 0.000 claims abstract description 260
- 238000000034 method Methods 0.000 claims abstract description 106
- 241001465754 Metazoa Species 0.000 claims abstract description 97
- 102000015736 beta 2-Microglobulin Human genes 0.000 claims abstract 20
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 494
- 239000002773 nucleotide Substances 0.000 claims description 284
- 125000003729 nucleotide group Chemical group 0.000 claims description 283
- 210000004027 cell Anatomy 0.000 claims description 233
- 108010061486 HLA-B27 Antigen Proteins 0.000 claims description 119
- 102000012153 HLA-B27 Antigen Human genes 0.000 claims description 113
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 claims description 104
- 241000283984 Rodentia Species 0.000 claims description 98
- 241000699670 Mus sp. Species 0.000 claims description 91
- 239000000427 antigen Substances 0.000 claims description 75
- 108091007433 antigens Proteins 0.000 claims description 75
- 102000036639 antigens Human genes 0.000 claims description 75
- 230000001086 cytosolic effect Effects 0.000 claims description 50
- 230000027455 binding Effects 0.000 claims description 48
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 44
- 108700043516 mouse H-2Kb Proteins 0.000 claims description 36
- 108700024394 Exon Proteins 0.000 claims description 32
- 101000937526 Mus musculus Beta-2-microglobulin Proteins 0.000 claims description 22
- 230000028993 immune response Effects 0.000 claims description 18
- 230000001105 regulatory effect Effects 0.000 claims description 17
- 150000007523 nucleic acids Chemical class 0.000 claims description 16
- 210000005260 human cell Anatomy 0.000 claims description 12
- 210000001161 mammalian embryo Anatomy 0.000 claims description 10
- 238000000338 in vitro Methods 0.000 claims description 9
- 210000004698 lymphocyte Anatomy 0.000 claims description 9
- 230000003013 cytotoxicity Effects 0.000 claims description 7
- 231100000135 cytotoxicity Toxicity 0.000 claims description 7
- 230000004048 modification Effects 0.000 claims description 6
- 238000012986 modification Methods 0.000 claims description 6
- 230000033228 biological regulation Effects 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 102000025850 HLA-A2 Antigen Human genes 0.000 claims 6
- 108010074032 HLA-A2 Antigen Proteins 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 1
- 210000002257 embryonic structure Anatomy 0.000 abstract description 14
- 210000000987 immune system Anatomy 0.000 abstract description 11
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 223
- 108090000623 proteins and genes Proteins 0.000 description 134
- 102000004169 proteins and genes Human genes 0.000 description 78
- 235000018102 proteins Nutrition 0.000 description 76
- 241000700159 Rattus Species 0.000 description 69
- 210000001744 T-lymphocyte Anatomy 0.000 description 68
- 108091054437 MHC class I family Proteins 0.000 description 63
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 63
- 102000047279 human B2M Human genes 0.000 description 62
- 230000014509 gene expression Effects 0.000 description 54
- 102000043129 MHC class I family Human genes 0.000 description 51
- 108020004414 DNA Proteins 0.000 description 47
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 47
- 108010075704 HLA-A Antigens Proteins 0.000 description 46
- 108091008874 T cell receptors Proteins 0.000 description 37
- 235000001014 amino acid Nutrition 0.000 description 34
- 230000008685 targeting Effects 0.000 description 34
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 32
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 27
- 125000003275 alpha amino acid group Chemical group 0.000 description 27
- 239000012634 fragment Substances 0.000 description 27
- 108700028369 Alleles Proteins 0.000 description 26
- 108010058607 HLA-B Antigens Proteins 0.000 description 26
- 206010028980 Neoplasm Diseases 0.000 description 26
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 23
- 210000000822 natural killer cell Anatomy 0.000 description 22
- 238000006467 substitution reaction Methods 0.000 description 22
- 201000010099 disease Diseases 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 19
- 239000013598 vector Substances 0.000 description 18
- 101000986086 Homo sapiens HLA class I histocompatibility antigen, A alpha chain Proteins 0.000 description 16
- 210000000612 antigen-presenting cell Anatomy 0.000 description 15
- 241000282412 Homo Species 0.000 description 13
- 102100025584 Leukocyte immunoglobulin-like receptor subfamily B member 1 Human genes 0.000 description 13
- 210000000349 chromosome Anatomy 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 12
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 11
- 108010052199 HLA-C Antigens Proteins 0.000 description 11
- 108010017736 Leukocyte Immunoglobulin-like Receptor B1 Proteins 0.000 description 11
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 11
- 230000000875 corresponding effect Effects 0.000 description 11
- 230000003993 interaction Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000002068 genetic effect Effects 0.000 description 9
- 102000007079 Peptide Fragments Human genes 0.000 description 8
- 108010033276 Peptide Fragments Proteins 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 108700019146 Transgenes Proteins 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 210000003719 b-lymphocyte Anatomy 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 230000006798 recombination Effects 0.000 description 7
- 238000005215 recombination Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 6
- 101000986087 Homo sapiens HLA class I histocompatibility antigen, B alpha chain Proteins 0.000 description 6
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 6
- 101150017040 I gene Proteins 0.000 description 6
- 241001529936 Murinae Species 0.000 description 6
- 101100338310 Mus musculus H2-D1 gene Proteins 0.000 description 6
- 230000030833 cell death Effects 0.000 description 6
- 210000005220 cytoplasmic tail Anatomy 0.000 description 6
- 210000004443 dendritic cell Anatomy 0.000 description 6
- 238000002744 homologous recombination Methods 0.000 description 6
- 230000006801 homologous recombination Effects 0.000 description 6
- 244000052637 human pathogen Species 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 206010022000 influenza Diseases 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 230000009258 tissue cross reactivity Effects 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 238000011714 129 mouse Methods 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 5
- 108010091938 HLA-B7 Antigen Proteins 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 230000030741 antigen processing and presentation Effects 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 238000011813 knockout mouse model Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
- 108091060290 Chromatid Proteins 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 241000712079 Measles morbillivirus Species 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 230000006044 T cell activation Effects 0.000 description 4
- 230000024932 T cell mediated immunity Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 238000009395 breeding Methods 0.000 description 4
- 230000001488 breeding effect Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 102000048974 human HLA-B Human genes 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 108010051219 Cre recombinase Proteins 0.000 description 3
- 108010086377 HLA-A3 Antigen Proteins 0.000 description 3
- 108090000144 Human Proteins Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- 108700005089 MHC Class I Genes Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 241000699729 Muridae Species 0.000 description 3
- 101100438957 Mus musculus Cd8a gene Proteins 0.000 description 3
- 108010091086 Recombinases Proteins 0.000 description 3
- 102000018120 Recombinases Human genes 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 108091023045 Untranslated Region Proteins 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000003393 splenic effect Effects 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 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 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 101001073212 Arabidopsis thaliana Peroxidase 33 Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 102100036008 CD48 antigen Human genes 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000011510 Elispot assay Methods 0.000 description 2
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 241000699694 Gerbillinae Species 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 2
- 101150118346 HLA-A gene Proteins 0.000 description 2
- 101150000578 HLA-B gene Proteins 0.000 description 2
- 108010024164 HLA-G Antigens Proteins 0.000 description 2
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 2
- 101000984190 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 1 Proteins 0.000 description 2
- 101001123325 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-beta Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical group OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 241001046461 Lophiomys imhausi Species 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 101150076359 Mhc gene Proteins 0.000 description 2
- 241000699669 Mus saxicola Species 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102100028961 Peroxisome proliferator-activated receptor gamma coactivator 1-beta Human genes 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 241000121210 Sigmodontinae Species 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 206010002022 amyloidosis Diseases 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003436 cytoskeletal effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002308 embryonic cell Anatomy 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 238000003205 genotyping method Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Chemical group OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 241001515942 marmosets Species 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 230000003584 silencer Effects 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- CNWINRVXAYPOMW-FCNJXWMTSA-N 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-biphosphate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCCC)COP(O)(=O)O[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H]1O CNWINRVXAYPOMW-FCNJXWMTSA-N 0.000 description 1
- 101150000874 11 gene Proteins 0.000 description 1
- 101710097567 12 kDa protein Proteins 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- 101100284398 Bos taurus BoLA-DQB gene Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108700031361 Brachyury Proteins 0.000 description 1
- 241000398949 Calomyscidae Species 0.000 description 1
- 241000700193 Calomyscus Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 206010008761 Choriomeningitis lymphocytic Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000398985 Cricetidae Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241001095404 Dipodoidea Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 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 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 101150043233 H2-D1 gene Proteins 0.000 description 1
- 101150026303 HEX1 gene Proteins 0.000 description 1
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 description 1
- 102100028966 HLA class I histocompatibility antigen, alpha chain F Human genes 0.000 description 1
- -1 HLA- B Proteins 0.000 description 1
- 102210042925 HLA-A*02:01 Human genes 0.000 description 1
- 108010059045 HLA-C*06 antigen Proteins 0.000 description 1
- 108010093013 HLA-DR1 Antigen Proteins 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 description 1
- 101000986080 Homo sapiens HLA class I histocompatibility antigen, alpha chain F Proteins 0.000 description 1
- 101100395310 Homo sapiens HLA-A gene Proteins 0.000 description 1
- 101000945335 Homo sapiens Killer cell immunoglobulin-like receptor 2DL5B Proteins 0.000 description 1
- 101000945339 Homo sapiens Killer cell immunoglobulin-like receptor 2DS2 Proteins 0.000 description 1
- 101000984206 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily A member 6 Proteins 0.000 description 1
- 101000984189 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 2 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 102100033628 Killer cell immunoglobulin-like receptor 2DL5B Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical group OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 102100025553 Leukocyte immunoglobulin-like receptor subfamily A member 6 Human genes 0.000 description 1
- 102100025583 Leukocyte immunoglobulin-like receptor subfamily B member 2 Human genes 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 108700005092 MHC Class II Genes Proteins 0.000 description 1
- 101710167887 Major outer membrane protein P.IA Proteins 0.000 description 1
- 108090000143 Mouse Proteins Proteins 0.000 description 1
- 101710164418 Movement protein TGB2 Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000398750 Muroidea Species 0.000 description 1
- 101000924587 Mus musculus Adenomatous polyposis coli protein Proteins 0.000 description 1
- 241001529466 Muscardinus avellanarius Species 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 241000282341 Mustela putorius furo Species 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 108091008877 NK cell receptors Proteins 0.000 description 1
- 102000027581 NK cell receptors Human genes 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 241000398990 Nesomyidae Species 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 101150037263 PIP2 gene Proteins 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 244000082204 Phyllostachys viridis Species 0.000 description 1
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241001338313 Platacanthomyidae Species 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101100262439 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UBA2 gene Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000398956 Spalacidae Species 0.000 description 1
- 101000874347 Streptococcus agalactiae IgA FC receptor Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000010782 T cell mediated cytotoxicity Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108700042075 T-Cell Receptor Genes Proteins 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000007238 Transferrin Receptors Human genes 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 108010004469 allophycocyanin Proteins 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 239000011425 bamboo Substances 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- HVCNNTAUBZIYCG-UHFFFAOYSA-N ethyl 2-[4-[(6-chloro-1,3-benzothiazol-2-yl)oxy]phenoxy]propanoate Chemical compound C1=CC(OC(C)C(=O)OCC)=CC=C1OC1=NC2=CC=C(Cl)C=C2S1 HVCNNTAUBZIYCG-UHFFFAOYSA-N 0.000 description 1
- 210000001808 exosome Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 108010052621 fas Receptor Proteins 0.000 description 1
- 102000018823 fas Receptor Human genes 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000009403 human autoimmunity Effects 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 210000000428 immunological synapse Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000010438 iron metabolism Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000001419 lymphocytic choriomeningitis Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- 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
- C07K14/70539—MHC-molecules, e.g. HLA-molecules
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0387—Animal model for diseases of the immune system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Environmental Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/793,812 US9591835B2 (en) | 2011-10-28 | 2013-03-11 | Genetically modified major histocompatibility complex animals |
| US13/793,812 | 2013-03-11 | ||
| PCT/US2014/023076 WO2014164640A1 (en) | 2013-03-11 | 2014-03-11 | Transgenic mice expressing chimeric major histocompatibility complex (mhc) class i molecules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20150131150A KR20150131150A (ko) | 2015-11-24 |
| KR102313053B1 true KR102313053B1 (ko) | 2021-10-18 |
Family
ID=50513441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020157028380A Active KR102313053B1 (ko) | 2013-03-11 | 2014-03-11 | 키메라 주요 조직적합성 복합체(ｍｈｃ) 제ｉ 부류 분자를 발현하는 유전자전이 마우스 |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP2967014B1 (enExample) |
| JP (1) | JP6456351B2 (enExample) |
| KR (1) | KR102313053B1 (enExample) |
| CN (1) | CN105188358B (enExample) |
| AU (2) | AU2014249150B2 (enExample) |
| CA (1) | CA2902543A1 (enExample) |
| ES (1) | ES2764829T3 (enExample) |
| WO (1) | WO2014164640A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| LT2958938T (lt) | 2013-02-20 | 2019-07-25 | Regeneron Pharmaceuticals, Inc. | Pelės, ekspresuojančios humanizuotus t ląstelių koreceptorius |
| EP2958937B1 (en) | 2013-02-22 | 2018-08-15 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized major histocompatibility complex |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| EP3209769B1 (en) * | 2014-10-24 | 2020-08-05 | The Board of Trustees of the Leland Stanford Junior University | Compositions and methods for inducing phagocytosis of mhc class i positive cells and countering anti-cd47/sirpa resistance |
| US10550187B2 (en) | 2014-10-24 | 2020-02-04 | Incept, Llc | Extra luminal scaffold |
| KR20240132525A (ko) | 2015-04-06 | 2024-09-03 | 리제너론 파아마슈티컬스, 인크. | 비인간 동물에서의 인간화 t 세포 매개 면역반응 |
| CN109456942A (zh) * | 2017-09-06 | 2019-03-12 | 亘喜生物科技（上海）有限公司 | 通用型嵌合抗原受体t细胞制备技术 |
| US20220340926A1 (en) * | 2019-05-27 | 2022-10-27 | Transgenic Inc. | Exon-humanized mouse |
| US10841728B1 (en) | 2019-10-10 | 2020-11-17 | Boomcloud 360, Inc. | Multi-channel crosstalk processing |
| CN113105555B (zh) * | 2020-01-10 | 2023-05-30 | 百奥赛图(北京)医药科技股份有限公司 | Mhc分子人源化的非人动物的构建方法及应用 |
| CN118511853A (zh) | 2021-03-31 | 2024-08-20 | 瑞泽恩制药公司 | 包含具有改善的tcrb组库多样性的人源化细胞免疫系统组分的基因修饰的小鼠 |
| EP4215042A1 (en) * | 2022-01-21 | 2023-07-26 | Max-Delbrück-Centrum für Molekulare Medizin | A non-human mammal comprising in its genome at least two human leukocyte antigen (hla) class i alleles, methods of making such mammal and uses thereof |
| WO2025212991A1 (en) | 2024-04-05 | 2025-10-09 | Regeneron Pharmaceuticals, Inc. | Rodent models of disease |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006639A1 (fr) | 2001-07-13 | 2003-01-23 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
| WO2005004592A2 (en) | 2003-07-30 | 2005-01-20 | Institut Pasteur | Transgenic mice having a human major histocompatibility complex (mhc) phenotype, experimental uses and applications |
| US20050050580A1 (en) | 2000-12-13 | 2005-03-03 | Masashi Gotoh | Transgenic animal expressing hla-a24 and utilization thereof |
| WO2008010100A2 (en) | 2006-07-13 | 2008-01-24 | Institut Pasteur | Immunodeficient mice transgenic for hla class i and hla class ii molecules and their uses |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5489742A (en) * | 1990-10-23 | 1996-02-06 | Board Of Regents, The University Of Texas System | Transgenic rats and animal models of inflammatory disease |
| US20020151690A1 (en) * | 1997-08-12 | 2002-10-17 | Luxemburg Alain T | Purification of antigen-specific t cells |
| EA200101125A1 (ru) * | 1999-04-23 | 2002-04-25 | Фармекса А/С | Способ понижающей регуляции активности il5 |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| CN1617888A (zh) * | 2002-01-18 | 2005-05-18 | 伊诺维奥埃斯 | 用于肌内给药的双特异性抗体dna的构建 |
| SE0301109D0 (sv) * | 2003-04-14 | 2003-04-14 | Mallen Huang | Nucleotide vaccine composition |
| PL2767161T3 (pl) | 2004-10-19 | 2018-09-28 | Regeneron Pharmaceuticals, Inc. | Sposób wytwarzania zwierzęcia homozygotycznego pod względem modyfikacji genetycznej |
| DK2770821T3 (da) * | 2011-10-28 | 2017-11-27 | Regeneron Pharma | Genetisk modificerede major histocompatibility-kompleks-mus |
-
2014
- 2014-03-11 WO PCT/US2014/023076 patent/WO2014164640A1/en not_active Ceased
- 2014-03-11 JP JP2016501146A patent/JP6456351B2/ja active Active
- 2014-03-11 ES ES14718226T patent/ES2764829T3/es active Active
- 2014-03-11 CA CA2902543A patent/CA2902543A1/en active Pending
- 2014-03-11 CN CN201480025263.6A patent/CN105188358B/zh active Active
- 2014-03-11 KR KR1020157028380A patent/KR102313053B1/ko active Active
- 2014-03-11 AU AU2014249150A patent/AU2014249150B2/en active Active
- 2014-03-11 EP EP14718226.5A patent/EP2967014B1/en active Active
-
2020
- 2020-07-01 AU AU2020204410A patent/AU2020204410C1/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050050580A1 (en) | 2000-12-13 | 2005-03-03 | Masashi Gotoh | Transgenic animal expressing hla-a24 and utilization thereof |
| WO2003006639A1 (fr) | 2001-07-13 | 2003-01-23 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
| WO2005004592A2 (en) | 2003-07-30 | 2005-01-20 | Institut Pasteur | Transgenic mice having a human major histocompatibility complex (mhc) phenotype, experimental uses and applications |
| WO2008010100A2 (en) | 2006-07-13 | 2008-01-24 | Institut Pasteur | Immunodeficient mice transgenic for hla class i and hla class ii molecules and their uses |
Non-Patent Citations (5)
| Title |
|---|
| Eur. J. Immunol., vol.19(12), pp.2349-2354(1989). |
| J. Exp. Med., vol.170(4), pp.1091-1101(1989). |
| J. Exp. Med., vol.173(4), pp.1007-1015(1991). |
| J. Immunol., vol.149(1), pp.136-142(1992). |
| Nature, vol. 348(6302), pp.642-644(1990.12.13). |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2016510998A (ja) | 2016-04-14 |
| KR20150131150A (ko) | 2015-11-24 |
| CN105188358A (zh) | 2015-12-23 |
| WO2014164640A1 (en) | 2014-10-09 |
| EP2967014B1 (en) | 2019-10-16 |
| CA2902543A1 (en) | 2014-10-09 |
| AU2014249150A1 (en) | 2015-09-24 |
| AU2020204410C1 (en) | 2023-02-02 |
| AU2020204410A1 (en) | 2020-07-23 |
| AU2020204410B2 (en) | 2022-11-24 |
| AU2014249150B2 (en) | 2020-04-02 |
| CN105188358B (zh) | 2018-01-26 |
| HK1212859A1 (en) | 2016-06-24 |
| EP2967014A1 (en) | 2016-01-20 |
| JP6456351B2 (ja) | 2019-01-23 |
| ES2764829T3 (es) | 2020-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10779520B2 (en) | Genetically modified major histocompatibility complex animals | |
| US20200375160A1 (en) | Genetically modified major histocompatibility complex mice | |
| AU2020204410C1 (en) | Transgenic mice expressing chimeric major histocompatibility complex (mhc) class i molecules | |
| AU2012324016B8 (en) | Genetically modified major histocompatibility complex mice | |
| HK1249712A1 (en) | Genetically modified major histocompatibility complex mice | |
| HK40106351A (en) | Genetically modified major histocompatibility complex mice | |
| RU2783984C2 (ru) | Генетически модифицированные в отношении главного комплекса гистосовместимости мыши | |
| HK40015797A (en) | Genetically modified major histocompatibility complex mice | |
| HK1212859B (en) | Transgenic mice expressing chimeric major histocompatibility complex (mhc) class i molecules |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20151008 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20190311 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20201130 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20210722 |
|
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20211008 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20211012 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20211022 |
|
| PR1001 | Payment of annual fee |