Cell子刊：浙江大学金勇丰/毛圆辉合作，通过mRNA-LNP介导的线粒体凋亡，增强过继T细胞疗法

Core Viewpoint - The article discusses a promising new strategy to enhance the efficacy of adoptive T cell therapy (ACT) for solid tumors by regulating mitochondrial apoptosis (mtApoptosis) in cancer cells, which has shown limited clinical effectiveness in this area [2][5]. Group 1: Research Findings - The research team developed an mRNA-based strategy that utilizes mRNA-lipid nanoparticles (LNP) to trigger strong mitochondrial apoptosis, thereby enhancing the anti-tumor immune response of ACT [5][7]. - This combined approach preferentially induces immunogenic cell death in cancer cells and reshapes the immunosuppressive microenvironment, leading to synergistic effects when used alongside ACT [5][7]. - The study revealed that this combination therapy enhances the cytotoxicity of endogenous T cells and alleviates T cell dysfunction induced by ACT, ultimately improving treatment outcomes [5][7]. Group 2: Mechanistic Insights - The core findings indicate that mRNA encoding BH3 activators can trigger mitochondrial apoptosis and enhance anti-tumor immunity [7]. - The combined strategy promotes the migration and multifunctionality of effector T cells, reprogramming them into a memory-like state and expanding T cell receptor (TCR) diversity [7][8]. - Overall, the research provides mechanistic insights into how activating mitochondrial apoptosis can enhance ACT [8].