肿瘤细胞治疗研究
英文原题：Challenges and recent advances in CAR-T cell therapy for solid tumors.
CAR-T 细胞疗法在血液系统恶性肿瘤中取得了革命性成功。
CAR-T（CAR-T）细胞疗法在血液系统恶性肿瘤中取得了突破性成功，但其广泛用于实体瘤治疗仍面临根本性挑战。本综述探讨 CAR-T 疗法攻克实体瘤时遇到的多重障碍，包括肿瘤抗原异质性、免疫抑制性肿瘤微环境（TME）、T 细胞浸润困难及治疗相关毒性。本文不仅描述这些挑战，也重点梳理近年来出现的突破性策略，涵盖新靶点（如 Claudin 18.2、B7-H3）、创新 CAR 设计（如逻辑门控 CAR、装甲型 CAR）、局部递送与原位生成技术，以及联合治疗（如联合放疗、免疫检查点抑制剂或溶瘤病毒）。最后，综述展望通过多学科整合开发智能、可控的新一代 CAR-T 技术，为推动该领域基础研究和临床转化提供参考。
Chimeric Antigen Receptor T-cell (CAR-T) therapy has achieved revolutionary success in hematological malignancies. However, its broad application in solid tumor treatment still faces fundamental challenges. This review explores the multiple obstacles encountered by CAR-T therapy in conquering solid tumors, including core issues such as tumor antigen heterogeneity, the immunosuppressive tumor microenvironment (TME), difficulties in T-cell infiltration, and treatment-related toxicities. Beyond merely describing these challenges, this article focuses on organizing the breakthrough strategies that have emerged in recent years. It highlights several cutting-edge directions, including the discovery of novel targets (e.g., Claudin 18.2, B7-H3), innovative CAR designs (e.g., logic-gated CARs, armored CARs), local delivery and in situ generation techniques, and combination therapies (e.g., with radiotherapy, immune checkpoint inhibitors, oncolytic viruses). Finally, this review outlines future directions of developing intelligent, controllable next-generation CAR-T technologies through multidisciplinary integration, hoping to provide a valuable perspective for advancing basic research and clinical translation in this field.
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