肿瘤细胞治疗研究
英文原题：CAR Beyond αβ T Cells: Unleashing NK Cells, Macrophages, and γδ T Lymphocytes Against Solid Tumors.
嵌合抗原受体（CAR）工程化细胞疗法代表了癌症免疫治疗的一项里程碑式进展。
嵌合抗原受体（CAR）工程化细胞疗法代表了癌症免疫治疗的一项里程碑式进展。尽管CAR-T疗法在血液系统恶性肿瘤中已展现出显著成功，但其在实体瘤中的疗效仍然受限，主要受制于抗原异质性、免疫抑制性微环境以及on-target/off-tumor毒性等因素。为克服这些局限，利用替代性免疫效应细胞（包括自然杀伤（NK）细胞、巨噬细胞和T淋巴细胞）的新兴CAR平台正迅速获得关注。本综述系统分析了CAR-NK、CAR-M和CAR-T细胞疗法的机制优势，同时批判性评估了临床转化中持续存在的挑战，包括细胞持久性有限、生产可扩展性以及动态免疫逃逸机制。我们进一步讨论了一些可行策略以增强治疗效果。通过将基础免疫学与转化工程学相衔接，本工作为开发能够应对实体瘤清除复杂性的CAR疗法提供了路线图。
Chimeric antigen receptor (CAR)-engineered cell therapy represents a landmark advancement in cancer immunotherapy. While CAR-T therapy has demonstrated remarkable success in hematological malignancies, its efficacy in solid tumors remains constrained mainly by factors such as antigen heterogeneity, immunosuppressive microenvironments, and on-target/off-tumor toxicity. To overcome these limitations, emerging CAR platforms that utilize alternative immune effectors, including natural killer (NK) cells, macrophages, and T lymphocytes, are rapidly gaining traction. This review systematically analyzes the mechanistic advantages of CAR-NK, CAR-M, and CAR- T cell therapies, while critically evaluating persistent challenges in clinical translation, including limited cell persistence, manufacturing scalability, and dynamic immune evasion mechanisms. We further discuss innovative strategies to enhance therapeutic efficacy through some viable strategies. By bridging fundamental immunology with translational engineering, this work provides a roadmap for developing CAR therapies capable of addressing the complexities of solid tumor eradication.
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