CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.
Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.
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尽管嵌合抗原受体(CAR)T 细胞疗法治疗部分 B 细胞淋巴瘤和白血病取得非凡成功,多种障碍仍限制其在实体瘤中的应用,因此研究人员开始探索能够制备治疗潜力更强 CAR-T 细胞的新方法。关于 CAR-T 临床疗效障碍的新认识显示,自噬可通过重编程细胞代谢塑造免疫应答,反之亦然。自噬是一种细胞“自我消化”过程,在溶酶体中降解和回收细胞内成分,并影响 T 细胞生物学,包括发育、存活、记忆形成和细胞代谢。本综述重点讨论自噬在调节和重塑 CAR-T 细胞代谢回路中的关键作用,以及 CAR-T 细胞和肿瘤微环境(TME)的代谢状态如何改变 CAR-T 细胞的自噬调控,从而恢复其在实体瘤 TME 中穿行时的功能能力。
Despite chimeric antigen receptor (CAR) T cell therapy's extraordinary success in subsets of B-cell lymphoma and leukemia, various barriers restrict its application in solid tumors. This has prompted investigating new approaches for producing CAR T cells with superior therapeutic potential. Emerging insights into the barriers to CAR T cell clinical success indicate that autophagy shapes the immune response via reprogramming cellular metabolism and vice versa.
Autophagy, a self-cannibalization process that includes destroying and recycling intracellular components in the lysosome, influences T cell biology, including development, survival, memory formation, and cellular metabolism. In this review, we will emphasize the critical role of autophagy in regulating and rewiring metabolic circuits in CAR T cells, as well as how the metabolic status of CAR T cells and the tumor microenvironment (TME) alter autophagy regulation in CAR T cells to restore functional competence in CAR Ts traversing solid TMEs.
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