Science重磅：in vivo CAR-T，在体内成功改造T细胞治疗癌症及自身免疫病，已开展临床试验

Core Viewpoint - The article discusses the development and potential of in vivo CAR-T cell therapy, particularly focusing on Capstan Therapeutics and its innovative approach to treating cancer and autoimmune diseases through a new mRNA delivery system [2][3][19]. Group 1: In Vivo CAR-T Technology - In vivo CAR-T technology allows for the generation of CAR-T cells directly within the body through the injection of lipid nanoparticles (LNP) delivering mRNA, addressing challenges such as complexity, time, and cost associated with traditional CAR-T therapies [2][3]. - Capstan Therapeutics, founded by leading researchers in the field, has secured $340 million in funding to advance this technology for various diseases [2][3]. Group 2: Clinical Trials and Research Findings - Capstan's CAR-T therapy CPTX2309 has commenced Phase 1 clinical trials for treating B cell-mediated autoimmune diseases [3]. - Preclinical studies demonstrated that the proprietary targeted lipid nanoparticles (tLNP) effectively delivered CAR mRNA to CD8+ T cells, showing promising therapeutic prospects and safety in animal models [3][4]. Group 3: Market Potential and Patient Demographics - The patient population for autoimmune diseases is significantly larger than that for B cell malignancies, with approximately 20 million individuals in the U.S. and 10% of the global population affected [6]. - There is a pressing need for scalable, off-the-shelf therapies that do not require chemotherapy preconditioning and can be administered in non-specialized medical centers [6]. Group 4: Mechanism and Efficacy - The research team developed a novel ionizable lipid L828 and optimized the LNP formulation to enhance targeting and accumulation in the liver while minimizing off-target effects [7]. - The CD8-L829-tLNP demonstrated a preference for modifying CD8+ T cells over CD4+ T cells, leading to effective targeting and destruction of B cells in both humanized mouse models and non-human primate models [9][10]. Group 5: Safety and Tolerability - In non-human primate studies, the treatment showed good tolerability, although some adverse effects were noted, such as a known side effect of CAR-T therapy [16]. - The study indicated that the treatment led to a temporary depletion of B cells, suggesting a reset of the immune system, which is crucial for long-term therapeutic benefits [16][19].