细胞因子
CD8型
过继性细胞移植
生物
免疫疗法
免疫系统
白细胞介素2
细胞生物学
免疫学
癌症研究
白细胞介素2受体
T细胞
细胞毒性T细胞
体外
生物化学
作者
Jonathan T. Sockolosky,Eleonora Trotta,Giulia Parisi,Lora K. Picton,Leon Su,Alan Le,Akanksha Chhabra,Stephanie Silveria,Benson M. George,Indigo King,Matthew Tiffany,Kevin Jude,Leah V. Sibener,David Baker,Judith A. Shizuru,Antoni Ribas,Jeffrey A. Bluestone,K. Christopher García
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2018-03-02
卷期号:359 (6379): 1037-1042
被引量:257
标识
DOI:10.1126/science.aar3246
摘要
Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal (ortho) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of orthoIL-2Rβ into T cells enabled the selective cellular targeting of orthoIL-2 to engineered CD4+ and CD8+ T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. OrthoIL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.
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