肿瘤细胞治疗研究
英文原题：Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.
嵌合抗原受体（CAR）-T 细胞疗法已成为一种变革性免疫治疗形式，使 T 细胞得以被精准工程化以识别并清除致病细胞。
嵌合抗原受体（CAR）T细胞疗法已成为一种变革性免疫疗法，可精准地工程化改造T细胞，使其识别并清除致病细胞。在血液系统恶性肿瘤中，靶向CD19或B细胞成熟抗原的CAR-T细胞已使既往难治性疾病患者获得显著缓解率和持久应答。尽管取得这些成功，将CAR-T疗法拓展至实体瘤仍面临挑战，原因包括抗原异质性、T细胞浸润不足和免疫抑制性肿瘤微环境（TME）。除肿瘤领域外，CAR-T疗法在自身免疫性疾病中也显示潜力；早期临床研究提示，靶向B细胞的CAR-T细胞可使系统性红斑狼疮等疾病持续缓解。本综述重点介绍CAR-T工程化进展，包括用于体外和体内编程的DNA及mRNA平台，并讨论增强CAR-T细胞迁移、持久性及抵抗TME的新兴策略。
Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond oncology, CAR-T cell therapy has also shown promise in autoimmune diseases, where early clinical studies suggest that B cell-directed CAR-T cells can induce sustained remission in conditions such as systemic lupus erythematosus. This review highlights advances in CAR-T cell engineering, including DNA- and mRNA-based platforms for ex vivo and in vivo programming, and discusses emerging strategies to enhance CAR-T cell trafficking, persistence, and resistance to TME.
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