Xu Xuequn, Gnanaprakasam J N Rashida, Sherman John, Wang Ruoning
Center for Childhood Cancer and Blood Diseases, Hematology/Oncology & BMT, The Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, United States.
Front Oncol. 2019 Apr 30;9:322. doi: 10.3389/fonc.2019.00322. eCollection 2019.
The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) through genetic engineering is one of the most promising new therapies for treating cancer patients. A robust CAR T cell-mediated anti-tumor response requires the coordination of nutrient and energy supplies with CAR T cell expansion and function. However, the high metabolic demands of tumor cells compromise the function of CAR T cells by competing for nutrients within the tumor microenvironment (TME). To substantially improve clinical outcomes of CAR T immunotherapy while treating solid tumors, it is essential to metabolically prepare CAR T cells to overcome the metabolic barriers imposed by the TME. In this review, we discuss a potential metabolism toolbox to improve the metabolic fitness of CAR T cells and maximize the efficacy of CAR T therapy.
通过基因工程进行表达嵌合抗原受体(CAR)的T细胞的过继性转移是治疗癌症患者最有前景的新疗法之一。强大的CAR T细胞介导的抗肿瘤反应需要营养和能量供应与CAR T细胞的扩增及功能相协调。然而,肿瘤细胞对高代谢的需求通过在肿瘤微环境(TME)中竞争营养物质而损害了CAR T细胞的功能。为了在治疗实体瘤时大幅改善CAR T免疫疗法的临床疗效,从代谢角度让CAR T细胞做好准备以克服TME带来的代谢障碍至关重要。在本综述中,我们讨论了一个潜在的代谢工具箱,以提高CAR T细胞的代谢适应性并最大化CAR T疗法的疗效。