肿瘤细胞治疗研究
英文原题：Engineering immunity with CAR-NK cells: advancing the frontiers of cancer immunotherapy.
嵌合抗原受体修饰的自然杀伤（CAR-NK）细胞正成为 CAR-T 疗法有前景的替代选择，具有毒性降低、异体可行性和生产灵活等优势。
嵌合抗原受体修饰的自然杀伤（CAR-NK）细胞作为CAR-T疗法的有前景替代方案正在兴起，具有毒性较低、适用于异体应用和生产灵活等优势。现有综述分别介绍NK细胞生物学和CAR工程进展，但缺少能将这些进展联系起来的统一视角。本综述提出新的综合框架，将具体肿瘤免疫逃逸机制（包括抗原丢失、谱系可塑性、抗原加工受损、表位遮蔽和胞啃作用）与相应的下一代CAR-NK工程解决方案对应起来。该“逃逸机制—解决方案”框架阐明双抗原CAR、低亲和力设计、NK细胞特异性信号、iPSC来源NK平台和多重基因编辑等创新，如何直接缓解已知导致治疗失败的机制。通过将肿瘤生物学与工程策略相连接，本综述为理性设计更灵活、更具韧性的CAR-NK疗法提供转化路线图。
Chimeric antigen receptor-modified natural killer (CAR-NK) cells are emerging as a promising alternative to CAR-T therapies, offering advantages such as reduced toxicity, allogeneic feasibility, and flexible manufacturing. Current reviews cover NK biology and CAR engineering progress, yet lack a unified perspective that connects these advances. This review provides a novel synthesis by mapping specific tumor immune evasion mechanisms, including antigen loss, lineage plasticity, impaired antigen processing, epitope masking, and trogocytosis to corresponding next-generation CAR-NK engineering solutions. This "evasion-to-solution" framework highlights how innovations such as dual-antigen CARs, low-affinity designs, NK-specific signaling, iPSC-derived NK platforms, and multiplex gene editing directly mitigate known mechanisms that lead to therapeutic failure. By linking tumor biology to engineering strategy, this review offers a translational roadmap for the rational design of more adaptable and resilient CAR-NK therapies.
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