Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Cell Biology, School of Basic Medical Sciences, Zhejiang University, Hangzhou, China.
Front Immunol. 2020 Jun 19;11:1046. doi: 10.3389/fimmu.2020.01046. eCollection 2020.
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 . 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.
嵌合抗原受体修饰 T 细胞（CAR-T）在治疗血液恶性肿瘤方面取得了令人瞩目的临床效果。然而，大量患者出现了复发，限制了 CAR-T 治疗的发展。这些复发的主要原因可归因于 CAR-T 细胞的持久性差和快速耗竭。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 的持久性或抵抗衰竭仍然是一个巨大的挑战。在这里，我们讨论了将胞质信号转导工程化作为 CAR 优化的重要策略。本综述总结了最近的进展，表明通过优化 CD3ζ 结构域或 CD28ζ CAR 的下游信号转导，可以提高 CAR-T 细胞的抗肿瘤功能。
