Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
Cancer Immunol Res. 2021 Aug;9(8):856-861. doi: 10.1158/2326-6066.CIR-21-0110.
The development of chimeric antigen receptor (CAR) T-cell therapy has led to a paradigm shift in cancer treatment. However, patients often do not benefit from CAR T-cell therapy due to poor persistence of the adoptively transferred cells. Development of strategies based on the generation and maintenance of long-lasting memory T cells may expand the therapeutic effects of CAR T cells. Mitochondrial metabolic pathways play crucial roles in regulating the fate, function, and longevity of T cells. Here, we discuss how reprogramming of mitochondrial metabolic pathways influences function, persistence, and determination of CAR T-cell fate toward a memory phenotype. Moreover, we explore how mitochondrial activity determines persistence and the clinical outcome of CAR T-cell therapy. In addition, we review some strategies for manipulating CAR T-cell mitochondria to improve the survival of CAR T cells.
嵌合抗原受体 (CAR) T 细胞疗法的发展导致了癌症治疗的范式转变。然而，由于过继转移细胞的持久性差，患者通常无法从 CAR T 细胞疗法中获益。基于生成和维持持久记忆 T 细胞的策略的发展可能会扩大 CAR T 细胞的治疗效果。线粒体代谢途径在调节 T 细胞的命运、功能和寿命方面发挥着关键作用。在这里，我们讨论了线粒体代谢途径的重编程如何影响 CAR T 细胞向记忆表型的功能、持久性和命运的决定。此外，我们探讨了线粒体活性如何决定 CAR T 细胞治疗的持久性和临床结果。此外，我们还回顾了一些操纵 CAR T 细胞线粒体的策略，以提高 CAR T 细胞的存活率。
