Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Int J Mol Sci. 2020 Sep 30;21(19):7222. doi: 10.3390/ijms21197222.
The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells. In this review, we summarize developments in universal or modular CAR T strategies that expand on current CAR T systems and open the door for more customizable T cell activity.
通过表达嵌合抗原受体 (CAR) 来对肿瘤相关抗原 (TAA) 进行 T 细胞工程改造,已显示出作为抗癌治疗方法的巨大潜力。用于灵活和模块化 CAR T 系统的策略正在加速发展,允许在细胞免疫治疗领域进行多种抗原靶向、精确编程和适应性解决方案。超越传统 CAR T 系统的固定抗原特异性,模块化 CAR T 技术通过使用开关分子将 T 细胞信号传导结构域和靶向元件分开。CAR T 细胞的活性取决于开关的存在,提供剂量滴定反应和对 CAR T 细胞的精确控制。在这篇综述中,我们总结了通用或模块化 CAR T 策略的发展,这些策略扩展了当前的 CAR T 系统,并为更可定制的 T 细胞活性开辟了道路。