Engineering Cytoplasmic Signaling of CD28ζ CARs for Improved Therapeutic Functions
Engineering Cytoplasmic Signaling of CD28ζ CARs for Improved Therapeutic Functions
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DOI：
10.3389/fimmu.2020.01046
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发表时间：
2020-06
影响因子：
7.3
通讯作者：
Xianhui Meng;Ruirui Jing;Liling Qian;Chun Zhou;Jie Sun
中科院分区：
文献类型：
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作者：
Xianhui Meng;Ruirui Jing;Liling Qian;Chun Zhou;Jie Sun
嵌合抗原受体修饰的T细胞（CAR-T）在治疗造血系统恶性肿瘤方面取得了令人印象深刻的临床结果。然而，大量患者出现复发，限制了CAR-T疗法的发展。这些复发的大多数潜在原因可归因于体内CAR-T细胞的持久性差和快速耗尽。尽管已经开发了多种策略，但如何在保持足够的细胞毒性功能的同时提高CAR-T持久性或抵抗耗竭仍然是一个巨大的挑战。在这里，我们讨论了工程胞质信号转导作为CAR优化的重要策略。本文综述了CAR-T细胞抗肿瘤功能的最新进展，这些进展表明可以通过优化CD 28 CAR的CD 3结构域或下游信号转导来提高CAR-T细胞的抗肿瘤功能。
Chimeric antigen receptor modified T cells (CAR-T) have yielded impressive clinical outcomes in treating hematopoietic malignancies. However, relapses have occurred in a substantial number of patients and limited the development of CAR-T therapy. Most underlying reasons for these relapses can be attributed to poor persistence and rapid exhaustion of CAR-T cells in vivo. Despite multiple strategies having been developed, how to improve CAR-T persistence or resist exhaustion while maintaining sufficient cytotoxic functions is still a great challenge. Here we discuss engineering cytoplasmic signaling as an important strategy for CAR optimization. This review summarizes recent advances showing that the anti-tumor function of CAR-T cells can be improved by optimizing the CD3ζ domain or downstream signaling of CD28ζ CAR.