JP2016506761A - ヒト化t細胞補助受容体を発現するマウス - Google Patents
ヒト化t細胞補助受容体を発現するマウス Download PDFInfo
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Abstract
Description
本出願は、2013年10月15日に出願された米国仮特許出願第61/890,915号および2013年2月20日に出願された米国仮特許出願第61/766,762号に対する利益を、35 U.S.C. §119(e)の下に主張し、これらの出願はその全体が参考として本明細書に援用される。
本明細書では、2014年2月20日に「2010794−0441_ST25」という名称のascii.txtファイルとして電子形式で提出された配列表に言及する。この.txtファイルは2014年2月13日に作成されたものであり、サイズは47kbである。
本発明は、ヒト化T細胞補助受容体を発現するように遺伝子操作された非ヒト動物(例えば、げっ歯類、例えばマウスまたはラット)に関する。本発明は、ヒト化CD4またはCD8補助受容体を発現するように遺伝子操作された非ヒト動物、ならびに当該補助受容体を発現する胚、組織、および細胞に関する。本発明は、さらに、ヒト化CD4補助受容体およびヒト化主要組織適合性遺伝子複合体(MHC)IIを同時発現するように工学的に操作された非ヒト動物に関する。本発明は、さらに、ヒト化CD8補助受容体およびヒト化MHC Iを同時発現するように工学的に操作された非ヒト動物に関する。ヒト化T細胞補助受容体(例えば、ヒト化CD4またはCD8)を発現する遺伝子操作された動物を作出するための方法も提供される。ヒト治療薬を開発するためにヒト化T細胞補助受容体を発現する遺伝子操作された動物を使用するための方法も提供される。
適応免疫応答では、外来抗原がBリンパ球上の受容体分子(例えば、免疫グロブリン)およびTリンパ球上の受容体分子(例えばT細胞受容体すなわちTCR)によって認識される。これらの外来抗原は、一般的に主要組織適合性遺伝子複合体(MHC)分子と称される特殊化されたタンパク質によって、細胞の表面上にペプチド断片として提示される。T細胞媒介性応答の間、MHC分子により提示される抗原はT細胞受容体によって認識される。しかし、有効な免疫応答のためには、MHC−抗原複合体のT細胞受容体認識を超えるものが必要である。T細胞補助受容体分子(例えば、CD4またはCD8)がMHCの不変部分に結合することも必要である。
本発明は、ヒト化T細胞補助受容体ポリペプチドを発現する遺伝子改変非ヒト動物(例えばマウス、ラット、ウサギなど);当該ポリペプチドを含む胚、細胞、および組織;それらを作出する方法;ならびにそれらの使用方法を提供する。別段の定義のない限り、本明細書で使用される全ての用語および句は、それに反することが明示されているまたはその用語もしくは句が使用される文脈から明らかである場合を除き、その用語および句が当技術分野において得ている意味を包含する。
遺伝子改変CD4動物
遺伝子改変CD8動物
遺伝子改変CD4動物および遺伝子改変CD8動物の使用
(実施例1)
遺伝子改変CD4マウスの構築および特徴付け
実施例1.1:キメラCD4遺伝子座の工学的操作
(実施例1.2)
遺伝子操作されたマウスにおけるキメラCD4の発現
(実施例2)
遺伝子改変CD8マウスの構築および特徴付け
(実施例2.1)
キメラCD8β遺伝子座の工学的操作
(実施例2.2)
キメラCD8α遺伝子座の工学的操作
(実施例2.3)
遺伝子操作されたマウスにおけるキメラCD8の発現
均等物
Claims (41)
- キメラヒト/非ヒトT細胞補助受容体ポリペプチドをコードするヌクレオチド配列を含み、
該キメラポリペプチドの非ヒト部分が、非ヒトT細胞補助受容体の少なくとも膜貫通ドメインおよび細胞質ドメインを含む、遺伝子改変非ヒト動物であって、
キメラT細胞補助受容体ポリペプチドを発現する非ヒト動物。 - 前記ヌクレオチド配列が内在性T細胞補助受容体遺伝子座に存在する、請求項1に記載の動物。
- 内在性遺伝子座に由来する機能的な内在性非ヒトT細胞補助受容体を発現しない、請求項1に記載の動物。
- 前記キメラT細胞補助受容体ポリペプチドが前記非ヒト動物のB細胞上で発現されない、請求項1に記載の動物。
- 前記T細胞補助受容体遺伝子座がCD4遺伝子座であり、前記T細胞補助受容体ポリペプチドがCD4である、請求項1に記載の動物。
- 前記キメラCD4ポリペプチドがB細胞またはCD8系列のT細胞上で発現されない、請求項5に記載の動物。
- 前記キメラT細胞補助受容体遺伝子座がCD8遺伝子座であり、前記T細胞補助受容体ポリペプチドがCD8α、CD8β、またはこれらの組合せから選択されるCD8ポリペプチドである、請求項1に記載の動物。
- CD8αポリペプチドおよびCD8βポリペプチドを含むキメラヒト/非ヒトCD8タンパク質を発現する、請求項7に記載の動物。
- 前記キメラCD8タンパク質がB細胞またはCD4系列のT細胞上で発現されない、請求項8に記載の動物。
- げっ歯類である、請求項1に記載の動物。
- マウスである、請求項10に記載の動物。
- キメラヒト/マウスCD4ポリペプチドをコードするヌクレオチド配列を含み、
前記キメラポリペプチドのヒト部分が、図1に記載されているヒトCD4ポリペプチドのドメインを少なくとも含み、
前記キメラポリペプチドのマウス部分が、マウスCD4ポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインを含む、遺伝子改変マウスであって、
キメラヒト/マウスCD4を発現するマウス。 - 前記ヒト部分が、前記ヒトCD4ポリペプチドの細胞外ドメインを含む、請求項12に記載のマウス。
- 前記ヌクレオチド配列が内在性CD4遺伝子座に存在する、請求項12に記載のマウス。
- 内在性マウスCD4遺伝子座に由来する機能的な内在性マウスCD4を発現しない、請求項12に記載のマウス。
- 前記ヌクレオチド配列がマウスプロモーター配列および調節配列に作動可能に連結している、請求項12に記載のマウス。
- 前記キメラCD4タンパク質がB細胞またはCD8系列のT細胞上で発現されない、請求項12に記載のマウス。
- ヒトまたはヒト化MHC IIタンパク質をさらに含み、該MHC IIタンパク質が、ヒトMHC IIαポリペプチドの細胞外ドメインおよびヒトMHC IIβポリペプチドの細胞外ドメインを含む、請求項12に記載のマウス。
- 前記ヌクレオチド配列が前記マウスの生殖細胞系列に含まれる、請求項12に記載のマウス。
- マウスのCD4遺伝子座を、キメラヒト/マウスCD4ポリペプチドを発現するように改変する方法であって、マウスの内在性CD4遺伝子座において、内在性マウスCD4ポリペプチドをコードするヌクレオチド配列をキメラヒト/マウスCD4ポリペプチドをコードするヌクレオチド配列で置き換えるステップを含む方法。
- 前記キメラヒト/マウスCD4ポリペプチドのヒト部分が、図1に記載されているヒトCD4ポリペプチドのドメインを少なくとも含み、内在性マウスCD4ポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインを含む、請求項20に記載の方法。
- 前記ヒト部分が、前記ヒトCD4ポリペプチドの細胞外ドメインを含む、請求項20に記載の方法。
- キメラヒト/マウスCD8αポリペプチドをコードする第1のヌクレオチド配列およびキメラヒト/マウスCD8βポリペプチドをコードする第2のヌクレオチド配列を含み、
該第1のヌクレオチド配列が、ヒトCD8αポリペプチドの細胞外ドメインならびにマウスCD8αポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインをコードする配列を含み、
該第2のヌクレオチド配列が、ヒトCD8βポリペプチドの細胞外ドメインならびにマウスCD8βポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインをコードする配列を含む、遺伝子改変マウスであって、
キメラヒト/マウスCD8タンパク質を発現するマウス。 - 前記第1のヌクレオチド配列および前記第2のヌクレオチド配列が、それぞれ内在性CD8α遺伝子座および内在性CD8β遺伝子座に存在する、請求項23に記載のマウス。
- 内在性CD8遺伝子座に由来する機能的な内在性CD8タンパク質を発現しない、請求項23に記載のマウス。
- 前記キメラヒト/マウスCD8タンパク質がB細胞またはCD4系列のT細胞上で発現されない、請求項23に記載のマウス。
- 前記第1のヌクレオチド配列がマウスCD8αプロモーター配列および調節配列に作動可能に連結しており、前記第2のヌクレオチド配列がマウスCD8βプロモーター配列および調節配列に作動可能に連結している、請求項23に記載のマウス。
- ヒトまたはヒト化MHC Iポリペプチドをさらに含み、該MHC IポリペプチドがヒトMHC Iポリペプチドの細胞外ドメインを含む、請求項23に記載のマウス。
- ヒトまたはヒト化β2ミクログロブリンポリペプチドをさらに含む、請求項28に記載のマウス。
- 前記第1のヌクレオチド配列および前記第2のヌクレオチド配列が前記マウスの生殖細胞系列に含まれる、請求項23に記載のマウス。
- マウスのCD8遺伝子座を、キメラヒト/マウスCD8ポリペプチドを発現するように改変する方法であって、マウスの内在性CD8遺伝子座において、内在性マウスCD8ポリペプチドをコードするヌクレオチド配列をキメラヒト/マウスCD8ポリペプチドをコードするヌクレオチド配列で置き換えるステップを含む方法。
- 前記CD8ポリペプチドがCD8α、CD8β、またはこれらの組合せから選択される、請求項31に記載の方法。
- 前記キメラヒト/マウスCD8ポリペプチドが、ヒトCD8ポリペプチドの細胞外ドメインならびに内在性マウスCD8ポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインを含む、請求項31に記載の方法。
- キメラヒト/マウスCD8αポリペプチドをコードするヌクレオチド配列を含み、
該キメラヒト/マウスCD8αポリペプチドが、ヒトCD8αポリペプチドの細胞外ドメインならびにマウスCD8αポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインを含む、遺伝子操作されたマウスであって、
キメラヒト/マウスCD8αポリペプチドを発現するマウス。 - 前記ヌクレオチド配列が内在性マウスCD8遺伝子座に存在する、請求項34に記載のマウス。
- 内在性CD8遺伝子座に由来する機能的な内在性CD8αポリペプチドを発現しない、請求項34に記載のマウス。
- 前記ヌクレオチド配列がマウスCD8αプロモーター配列および調節配列に作動可能に連結している、請求項34に記載のマウス。
- キメラヒト/マウスCD8βポリペプチドをコードするヌクレオチド配列を含み、
該キメラヒト/マウスCD8βポリペプチドが、ヒトCD8βポリペプチドの細胞外ドメインならびにマウスCD8βポリペプチドの少なくとも膜貫通ドメインおよび細胞質ドメインを含む、遺伝子操作されたマウスであって、
キメラヒト/マウスCD8βポリペプチドを発現するマウス。 - 前記ヌクレオチド配列が内在性マウスCD8遺伝子座に存在する、請求項38に記載のマウス。
- 内在性CD8遺伝子座に由来する機能的な内在性CD8βポリペプチドを発現しない、請求項38に記載のマウス。
- 前記ヌクレオチド配列がマウスCD8βプロモーター配列および調節配列に作動可能に連結している、請求項38に記載のマウス。
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Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
CA2852962C (en) | 2011-10-28 | 2022-05-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing chimeric major histocompatibility complex (mhc) ii molecules |
RS56656B1 (sr) | 2011-10-28 | 2018-03-30 | Regeneron Pharma | Miševi sa genetski modifikovanim glavnim kompleksom gena tkivne podudarnosti |
KR102579405B1 (ko) * | 2013-02-20 | 2023-09-18 | 리제너론 파아마슈티컬스, 인크. | 사람화된 t-세포 보조-수용체를 발현하는 마우스 |
KR102211267B1 (ko) | 2013-02-22 | 2021-02-04 | 리제너론 파아마슈티컬스, 인크. | 사람화된 주요 조직적합성 복합체를 발현하는 마우스 |
US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
LT3175706T (lt) | 2013-09-23 | 2019-02-25 | Regeneron Pharmaceuticals, Inc. | Gyvūnai, išskyrus žmogų, turintys humanizuotą signalą reguliuojančio baltymo geną |
KR102223264B1 (ko) | 2014-04-08 | 2021-03-09 | 리제너론 파아마슈티컬스, 인크. | 인간화된 Fc-감마 수용체를 갖는 비-인간 동물 |
NO2785538T3 (ja) | 2014-05-07 | 2018-08-04 | ||
MX2016016903A (es) | 2014-06-19 | 2017-03-27 | Regeneron Pharma | Animales no humanos que tienen un gen de muerte celular programada 1 humanizado. |
CA2959428A1 (en) | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
SI3223605T1 (sl) * | 2014-11-24 | 2021-03-31 | Regeneron Pharmaceuticals, Inc. | Nehumane živali, ki izražajo humaniziran CD3 kompleks |
NZ731471A (en) | 2014-12-05 | 2021-12-24 | Regeneron Pharma | Non-human animals having a humanized cluster of differentiation 47 gene |
US9913461B2 (en) * | 2014-12-09 | 2018-03-13 | Regeneron Pharmaceuticals, Inc. | Genetically modified mouse whose genome comprises a humanized CD274 gene |
MX2017012829A (es) | 2015-04-06 | 2018-02-23 | Regeneron Pharma | Respuestas inmunitarias mediadas por células t humanizadas en animales no humanos. |
MA44907A (fr) * | 2015-09-11 | 2018-07-18 | Agenus Inc | Cellules hôtes génétiquement modifiées et leurs procédés d'utilisation |
MX2018005389A (es) | 2015-11-20 | 2018-09-05 | Regeneron Pharma | Animales no humanos que tienen un gen 3 de activacion linfocitaria humanizado. |
US10070632B2 (en) | 2016-02-29 | 2018-09-11 | Regeneron Pharmaceuticals, Inc. | Rodents having a humanized TMPRSS gene |
WO2017150763A1 (ko) * | 2016-02-29 | 2017-09-08 | (주)메디톡스 | 인간 cd3 발현 동물모델 및 이의 용도 |
CN113907043B (zh) | 2016-06-03 | 2023-08-01 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
SG11202002456WA (en) | 2017-11-30 | 2020-04-29 | Regeneron Pharma | Non-human animals comprising a humanized trkb locus |
AU2019242586A1 (en) | 2018-03-26 | 2020-10-01 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
CA3097396A1 (en) * | 2018-04-19 | 2019-10-24 | Baylor College Of Medicine | Reprogramming cd4 t cells into cytotoxic cd8 cells by forced expression of cd8ab and class 1 restricted t cell receptors |
WO2020018511A1 (en) | 2018-07-16 | 2020-01-23 | Regeneron Pharmaceuticals, Inc. | Non-human animal models of ditra disease and uses thereof |
AU2022249328A1 (en) | 2021-03-31 | 2023-09-21 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice comprising humanized cellular immune system components with improved diversity of tcrβ repertoire |
WO2024064860A1 (en) | 2022-09-22 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing components of human cellular immune system |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070209083A1 (en) * | 2001-07-13 | 2007-09-06 | Genoway | Cell and transgenic animal modelling human antigenic presentation and their uses |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5958678A (en) * | 1986-08-21 | 1999-09-28 | The Trustees Of Columbia University In The City Of New York | DNA encoding the T cell surface protein T4 and use of fragments of T4 in the treatment of AIDS |
ATE423195T1 (de) | 1989-07-25 | 2009-03-15 | Cell Genesys Inc | Homologe rekombination für universelle donorzellen und chimerische säugetierzellen |
US5574205A (en) | 1989-07-25 | 1996-11-12 | Cell Genesys | Homologous recombination for universal donor cells and chimeric mammalian hosts |
US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US7041871B1 (en) * | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
GB9100481D0 (en) | 1991-01-10 | 1991-02-20 | Inst Nat Sante Rech Med | Genetically engineered mice |
AU2661692A (en) | 1991-09-19 | 1993-04-27 | President And Fellows Of Harvard College | Transgenic mhc class i and class ii antigen-deficient mammals |
WO1994006908A1 (en) | 1992-09-11 | 1994-03-31 | The Regents Of The University Of California | Transgenic non-human animals having targeted lymphocyte transduction genes |
US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
GB9315303D0 (en) | 1993-07-23 | 1993-09-08 | Zeneca Ltd | Polypeptide |
US5965787A (en) | 1995-08-31 | 1999-10-12 | Mayo Foundation For Medical Education And Research | HLA-DRBI peptides with specific binding affinity for HLA-DQ molecules: prevention and treatment of rheumatoid arthritis |
US6002066A (en) | 1996-01-16 | 1999-12-14 | Ortho Pharmaceutical Corp. | H2-M modified transgenic mice |
WO1997032603A1 (en) | 1996-03-05 | 1997-09-12 | The Scripps Research Institute | Recombinant constructs encoding t cell receptors specific for human hla-restricted tumor antigens |
CA2616914C (en) | 1996-12-03 | 2012-05-29 | Abgenix, Inc. | Egfr-binding antibody |
WO1999014236A1 (en) | 1997-09-16 | 1999-03-25 | Oregon Health Sciences University | Recombinant mhc molecules useful for manipulation of antigen-specific t-cells |
US6372955B1 (en) | 1998-02-17 | 2002-04-16 | Ortho Mcneil Pharmaceutical, Inc. | Methods for Producing B cells and antibodies from H2-O modified transgenic mice |
AU1023401A (en) | 1999-10-12 | 2001-04-23 | Institut Pasteur | Design of a polyepitopic construct for the induction of hla-a2.1 restricted hiv 1 specific ctl responses using hhd mice |
US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
JPWO2002047474A1 (ja) | 2000-12-13 | 2004-04-15 | 住友製薬株式会社 | Hla−a24発現トランスジェニック動物及びその利用 |
DK1409646T3 (da) | 2000-12-19 | 2012-08-06 | Altor Bioscience Corp | Transgene dyr omfattende et humaniseret immunsystem |
WO2002092773A2 (en) * | 2001-05-15 | 2002-11-21 | Ortho-Mcneil Pharmaceutical, Inc. | Ex-vivo priming for generating cytotoxic t lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease |
US7663017B2 (en) | 2003-07-30 | 2010-02-16 | Institut Pasteur | Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications |
JP4857450B2 (ja) | 2004-03-09 | 2012-01-18 | 財団法人名古屋産業科学研究所 | ヒト関節リウマチの病態を再現するトランスジェニック非ヒト哺乳動物 |
DK2767161T3 (en) | 2004-10-19 | 2018-05-07 | Regeneron Pharma | Method of generating an animal homozygous for genetic modification |
EP1878798A1 (en) | 2006-07-13 | 2008-01-16 | Institut Pasteur | Method of producing a multichimeric mouse and applications to study the immunopathogenesis of human tissue-specific pathologies |
EP1878342A1 (en) | 2006-07-13 | 2008-01-16 | Institut Pasteur | Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses |
TWI476280B (zh) | 2008-03-07 | 2015-03-11 | Regeneron Pharma | 來自二倍體宿主胚胎注射之es-細胞衍生的老鼠 |
DK2708559T3 (en) * | 2008-04-11 | 2018-06-14 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of repeatedly binding two or more antigen molecules |
US20090328240A1 (en) | 2008-06-24 | 2009-12-31 | Sing George L | Genetically modified mice as predictors of immune response |
AU2009298458B2 (en) * | 2008-09-30 | 2015-10-08 | Ablexis, Llc | Non-human mammals for the production of chimeric antibodies |
US9277999B2 (en) * | 2009-02-27 | 2016-03-08 | University of Pittsburgh—of the Commonwealth System of Higher Education | Joint bioscaffolds |
HUE055817T2 (hu) | 2009-07-08 | 2021-12-28 | Kymab Ltd | Állatmodellek és terápiás molekulák |
GB2472108B (en) * | 2009-08-27 | 2011-07-13 | Budha Singh Dhinjan | Wall bead |
SI3095871T1 (sl) * | 2010-02-08 | 2019-06-28 | Regeneron Pharmaceuticals, Inc. | Miš z navadno lahko verigo |
WO2011100761A2 (en) * | 2010-02-15 | 2011-08-18 | Indiana University Research And Technology Corporation | Cd4 t-cells involved in mammalian host response to epithelial cell infection and uses thereof |
SA111320266B1 (ar) * | 2010-03-11 | 2015-06-21 | رينات نيوروساينس كوربوريشن | أجسام مضادة مع ارتباط مولد مضاد يعتمد على الأس الهيدروجيني |
US9557323B2 (en) | 2010-09-24 | 2017-01-31 | The United States Of America As Represented By The Secretary Of The Navy | Humanized transgenic mouse model |
US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
RS56656B1 (sr) | 2011-10-28 | 2018-03-30 | Regeneron Pharma | Miševi sa genetski modifikovanim glavnim kompleksom gena tkivne podudarnosti |
CA2852962C (en) | 2011-10-28 | 2022-05-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing chimeric major histocompatibility complex (mhc) ii molecules |
KR102579405B1 (ko) * | 2013-02-20 | 2023-09-18 | 리제너론 파아마슈티컬스, 인크. | 사람화된 t-세포 보조-수용체를 발현하는 마우스 |
US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
KR102211267B1 (ko) | 2013-02-22 | 2021-02-04 | 리제너론 파아마슈티컬스, 인크. | 사람화된 주요 조직적합성 복합체를 발현하는 마우스 |
JP6456351B2 (ja) | 2013-03-11 | 2019-01-23 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | キメラ主要組織適合複合体(mhc)クラスi分子を発現する遺伝子導入マウス |
MX2017012829A (es) | 2015-04-06 | 2018-02-23 | Regeneron Pharma | Respuestas inmunitarias mediadas por células t humanizadas en animales no humanos. |
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