嵌合抗原受体T细胞的代谢优化★

Metabolic optimization of chimeric antigen receptor T cells★

摘要:

基因工程设计的嵌合抗原受体（CAR）T细胞对血液肿瘤的治疗取得了显著成效，但对实体肿瘤的疗效有限。肿瘤异质性、肿瘤微环境的代谢挑战和免疫抑制导致了CAR-T细胞的功能障碍，造成了CAR-T细胞疗法对实体肿瘤的治疗困境。本文综述了CAR-T细胞结构、CAR-T细胞制备和涉及的信号通路，简述了乳酸、谷氨酰胺和葡萄糖等代谢物对CAR-T细胞的影响。此外，本文还从CAR-T细胞设计、体内外扩增条件和克服CAR-T细胞治疗的毒性效应三个角度概括CAR-T细胞治疗的最新进展。通过对CAR-T细胞的代谢优化，打破传统CAR-T细胞治疗的局限性，突破其现有的肿瘤类型限制。

Abstract:

Genetically engineered chimeric antigen receptor (CAR) T cells have achieved remarkable success in the treatment of haematological tumors, but have limited efficacy against solid tumors. Tumor heterogeneity, metabolic challenges in the tumor microenvironment and immunosuppression have resulted in CAR-T cell dysfunction, which has caused the therapeutic dilemma of CAR-T cell therapy for solid tumors. This paper reviewed the CAR-T cell structure, CAR-T cell preparation and the involved signaling pathways, and briefly summarized the effects of metabolites such as lactate, glutamine and glucose on CAR-T cells. In addition, this paper outlined three perspectives on recent advances in CAR-T cell therapy, including CAR-T cell design, ex vivo and in vivo expansion conditions, and overcoming toxic effects of CAR-T therapy. By optimizing the metabolism of CAR-T cells, the limitations of conventional CAR-T cell therapy will be overcome, which will enable CAR-T cell therapy to break through the limitations of tumor types.