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Cell子刊:复旦大学骆菲菲/储以微团队开发新型CAR-T细胞疗法,提高对实体瘤的治疗效果
生物世界·2025-05-06 07:45

Core Viewpoint - CAR-T cell therapy has shown remarkable efficacy in treating hematological cancers, but its effectiveness in solid tumors remains limited due to the challenging tumor microenvironment (TME) [1][2] Group 1: Research Findings - The study reveals that Foxp3 enhances the long-term efficacy of CAR-T cells through metabolic reprogramming, providing a survival advantage in solid tumor environments [2][7] - CAR-T Foxp3 cells exhibit a distinct metabolic reprogramming profile compared to conventional CAR-T cells, characterized by decreased aerobic glycolysis and oxidative phosphorylation, alongside increased lipid metabolism [5][9] - The interaction between Foxp3 and Drp1 drives the metabolic transition in CAR-T Foxp3 cells, which do not acquire the immunosuppressive functions typical of Treg cells [5][9] Group 2: Implications for Cancer Treatment - The findings establish a new strategy based on metabolic reprogramming to enhance CAR-T cell adaptability in harsh tumor microenvironments while maintaining therapeutic efficacy [9] - CAR-T Foxp3 cells demonstrate lower levels of exhaustion markers and exhibit stronger anti-tumor efficacy compared to traditional CAR-T cells [9][6]