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模块化嵌合抗原受体系统用于通用 CAR T 细胞重定向。

Modular Chimeric Antigen Receptor Systems for Universal CAR T Cell Retargeting.

机构信息

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.

出版信息

Int J Mol Sci. 2020 Sep 30;21(19):7222. doi: 10.3390/ijms21197222.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c486/7582510/0b6b65e60fe0/ijms-21-07222-g001.jpg

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