JP6192537B2 - Ｔ細胞の標的抗原の同定 - Google Patents
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| US10066265B2 (en) | 2014-04-01 | 2018-09-04 | Adaptive Biotechnologies Corp. | Determining antigen-specific t-cells |
| RS62471B1 (sr) | 2014-04-16 | 2021-11-30 | Juno Therapeutics Gmbh | Metode, kompleti i uređaji za proširenje populacije ćelija |
| IL292038B2 (en) | 2014-04-23 | 2024-12-01 | Juno Therapeutics Inc | Methods for enriching or producing immune cell populations for adoptive therapy |
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| CA2966201A1 (en) | 2014-10-29 | 2016-05-06 | Adaptive Biotechnologies Corp. | Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from many samples |
| US10246701B2 (en) | 2014-11-14 | 2019-04-02 | Adaptive Biotechnologies Corp. | Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture |
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| EP3277294B1 (en) | 2015-04-01 | 2024-05-15 | Adaptive Biotechnologies Corp. | Method of identifying human compatible t cell receptors specific for an antigenic target |
| EP3112375A1 (en) * | 2015-07-03 | 2017-01-04 | Ludwig-Maximilians-Universität München | Antigenic peptides for the diagnosis, therapy monitoring and/or treatment of psoriasis vulgaris |
| AU2016326734B2 (en) * | 2015-09-25 | 2022-07-07 | Abvitro Llc | High throughput process for T cell receptor target identification of natively-paired T cell receptor sequences |
| RU2761555C2 (ru) | 2015-10-22 | 2021-12-09 | Джуно Терапьютикс Гмбх | Способы, наборы, средства и устройства для трансдукции |
| KR102908806B1 (ko) | 2015-10-22 | 2026-01-07 | 주노 테라퓨틱스 게엠베하 | 세포의 배양 방법 및 이를 위한 키트와 장치 |
| MA45489A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés de culture de cellules, kits et appareil associés |
| EP3368691A4 (en) * | 2015-10-27 | 2019-04-03 | Arizona Board of Regents on behalf of Arizona State University | HIGH-SCREEN-TYPE IDENTIFICATION OF ANTIGENES AND EPITOPES FOR T-CELL DETECTION |
| MX2018006789A (es) | 2015-12-03 | 2019-02-13 | Juno Therapeutics Inc | Receptores quimericos modificados y composiciones y metodos relacionados. |
| WO2018053374A2 (en) * | 2016-09-16 | 2018-03-22 | Memorial Sloan Kettering Cancer Center | Methods and compositions for t-cell epitope screening |
| US10428325B1 (en) | 2016-09-21 | 2019-10-01 | Adaptive Biotechnologies Corporation | Identification of antigen-specific B cell receptors |
| KR102606929B1 (ko) * | 2016-11-07 | 2023-11-27 | 제노비에 에이비 | 동족 항원과 t-세포 수용체 상호작용의 발견 및 특징규명을 위한 조작된 2-부분 세포 디바이스 |
| EP4332232A3 (en) * | 2016-11-07 | 2024-05-08 | Genovie AB | An engineered multi-component system for identification and characterisation of t-cell receptors and t-cell antigens |
| EP3535393B1 (en) | 2016-11-07 | 2021-09-22 | Genovie AB | A two-part device for t-cell receptor synthesis and stable genomic integration to tcr-presenting cells |
| AU2018260380B2 (en) | 2017-04-27 | 2025-02-13 | Juno Therapeutics Gmbh | Oligomeric particle reagents and methods of use thereof |
| WO2018213803A1 (en) * | 2017-05-19 | 2018-11-22 | Neon Therapeutics, Inc. | Immunogenic neoantigen identification |
| WO2019069125A1 (en) | 2017-10-06 | 2019-04-11 | Oslo Universitetssykehus Hf | CHIMERIC ANTIGEN RECEPTORS |
| US11254980B1 (en) | 2017-11-29 | 2022-02-22 | Adaptive Biotechnologies Corporation | Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements |
| AU2019256536C1 (en) | 2018-04-19 | 2026-01-15 | Baylor College Of Medicine | Reprogramming CD4 T cells into cytotoxic CD8 cells by forced expression of CD8αβ and Class 1 restricted T cell receptors |
| BR112021002390A2 (pt) | 2018-08-09 | 2021-05-11 | Juno Therapeutics Inc | processos para gerar células modificadas e suas composições |
| EP3842550A4 (en) * | 2018-08-24 | 2022-06-29 | Repertoire Genesis Incorporation | Method for analyzing functional subunit pair gene of t cell receptor and b cell receptor |
| WO2020089343A1 (en) | 2018-10-31 | 2020-05-07 | Juno Therapeutics Gmbh | Methods for selection and stimulation of cells and apparatus for same |
| KR102769935B1 (ko) * | 2021-03-30 | 2025-02-19 | 한국과학기술원 | 펩타이드-mhc에 대한 t 세포 활성의 예측 방법 및 분석장치 |
| CN114807125B (zh) * | 2022-05-20 | 2023-09-12 | 纳昂达(南京)生物科技有限公司 | 测序文库接头、测序文库及其构建方法、提升ngs建库连接效率的方法 |
| CN121100267A (zh) | 2022-12-09 | 2025-12-09 | 朱诺治疗学股份有限公司 | 使用全息成像预测细胞表型的机器学习方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6037135A (en) | 1992-08-07 | 2000-03-14 | Epimmune Inc. | Methods for making HLA binding peptides and their uses |
| US20010053523A1 (en) * | 1995-06-02 | 2001-12-20 | M&E Biotech A/S. | Method for identification of biologically active peptides and nucleic acids |
| JP2000505650A (ja) * | 1996-02-08 | 2000-05-16 | アメリカ合衆国 | 樹状突起細胞を形質転換し、そしてｔ細胞を活性化するための方法及び組成物 |
| WO1998046739A1 (fr) * | 1997-04-16 | 1998-10-22 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Molecules immunomodulatrices et leur procede de production |
| US6872518B2 (en) * | 1997-09-22 | 2005-03-29 | University Of Rochester | Methods for selecting polynucleotides encoding T cell epitopes |
| DE10009341A1 (de) * | 2000-02-22 | 2001-09-06 | Florian Kern | Verfahren zur antigen-spezifischen Stimulation von T-Lymphozyten |
| JP4812951B2 (ja) * | 2001-03-21 | 2011-11-09 | 一般財団法人化学及血清療法研究所 | 特異性不明のｔ細胞のクローン化法及びその認識ペプチドリガンドの同定方法 |
| CA2445181A1 (fr) * | 2001-04-13 | 2002-10-24 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Procede d'analyse des lymphocytes t par le biais des recepteurs des lymphocytes t d'un organisme |
| US20030003485A1 (en) * | 2001-05-15 | 2003-01-02 | Ludwig Institute For Cancer Research | Methods for identifying antigens |
| WO2003068800A2 (en) | 2002-02-13 | 2003-08-21 | Ludwig Institute For Cancer Research | Isolated peptides which bind to hla molecules and uses thereof |
| JP2009515534A (ja) * | 2005-11-10 | 2009-04-16 | ザ ユニヴァーシティー オヴ シカゴ | Ｈｃｖ−反応性ｔ細胞受容体 |
| JP5292550B2 (ja) * | 2007-03-23 | 2013-09-18 | 静岡県 | Ｔ細胞レセプターβ鎖遺伝子及びα鎖遺伝子 |
| GB0712670D0 (en) * | 2007-06-29 | 2007-08-08 | King S College London | Isolated peptides and uses thereof |
| CN102066578B (zh) * | 2008-04-16 | 2016-07-06 | 哈森阿尔法生物技术研究院 | 用于评价和比较免疫组库的方法 |
| US7892202B2 (en) | 2008-05-09 | 2011-02-22 | Merit Medical Systems, Inc. | System and method for inflation syringe with improved display |
| EP2364368B1 (en) * | 2008-11-07 | 2014-01-15 | Sequenta, Inc. | Methods of monitoring conditions by sequence analysis |
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| EP3376225A1 (en) | 2018-09-19 |
| US20130195900A1 (en) | 2013-08-01 |
| CA2806440A1 (en) | 2012-02-09 |
| EP2982766B1 (en) | 2018-05-23 |
| EP2982766A1 (en) | 2016-02-10 |
| JP2013535209A (ja) | 2013-09-12 |
| EP2601521B1 (en) | 2018-05-02 |
| WO2012017081A1 (en) | 2012-02-09 |
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