使用合成受体设计具有定制的治疗反应程序的T细胞
Kole T Roybal1, Jasper Z Williams1, Leonardo Morsut1
1Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; UCSF Center for Systems and Synthetic Biology, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, San Francisco, CA 94158, USA.
Cell
|October 4, 2016
概括
工程T细胞可以使用合成Notch (synNotch) 受体进行定制,以改善癌症治疗. 这项技术可以精确控制免疫反应,提高对瘤的安全性和有效性.
科学领域:
- 免疫学
- 合成生物学
- 生物技术
背景情况:
- 治疗T细胞的有效性受到自然免疫反应的限制,这些免疫反应可能是有毒的或不足以克服瘤免疫抑制.
- 通过精确控制它们的反应和安全性, 可以改善目前的工程T细胞疗法.
研究的目的:
- 研究合成Notch (synNotch) 受体的使用,以塑造定制的免疫细胞反应.
- 展示synNotch技术在增强基于T细胞的疗法的潜力.
主要方法:
- 具有能够识别抗原的synNotch受体的初级T细胞.
- 通过 synNotch 信号传递来诱导对特定抗原的转录激活.
- 分析定制的细胞因子分泌,T细胞分化和有效载荷传递.
主要成果:
- 在T细胞中,SynNotch受体启用了定制反应程序,包括定制的细胞因子分泌.
- 已经证明T细胞有偏差分化和局部传递抗体等治疗有效载荷.
- SynNotch T细胞成功地识别了抗原并重塑了当地的微环境.
结论:
- 合成口受体为工程T细胞功能提供了多功能平台.
- 这项技术可以通过定制免疫反应来提高T细胞治疗的安全性和有效性.
- SynNotch T细胞提供了一种可通用的方法来准和修改与疾病相关的微环境.
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