[摘 要] 嵌合抗原受体自然杀伤细胞（CAR-NK细胞）疗法作为一种新兴的细胞免疫治疗策略，凭借其高安全性和“现货化”制 备的独特优势，展现出比CAR-T细胞疗法更为广阔的临床应用潜力。本文深入论述了CAR-NK细胞的抗肿瘤机制，详细剖析了 其靶向识别机制、固有杀伤活性，以及通过特异性受体优化以增强其在肿瘤微环境中的适应能力的最新进展。对CAR-NK细胞 的多种细胞来源，包括外周血、脐带血、诱导多能干细胞（iPSC）及NK-92细胞等的优势与挑战进行了深入讨论，并总结了其在肿 瘤免疫微环境中面临的持久性不足、免疫抑制，以及抗原异质性等主要瓶颈，提出了CAR-NK细胞治疗实体瘤的优势、局限性及 未来发展与临床应用的方向。

[Abstract] Chimeric antigen receptor natural killer (CAR-NK) cell therapy, as an emerging cellular immunotherapy strategy, has demonstrated a broader clinical application potential compared to CAR-T cell therapy due to its high safety profile and the unique advantages of 'off-the-shelf ' preparation. This article thoroughly discusses the antitumor mechanisms of CAR-NK cells, elucidating their targeted recognition mechanism, inherent cytotoxic activity, and the latest advancements in optimizing specific receptors to enhance their adaptability within the tumor microenvironment. Additionally, it provides an in-depth analysis of the advantages and challenges of various sources for CAR-NK cells, including peripheral blood, umbilical cord blood, induced pluripotent stem cells (iPSCs), and NK-92 cells, while summarizing their major challenges in the tumor immune microenvironment, such as insufficient persistence, immune suppression, and antigen heterogeneity. Finally, this article presents the therapeutic potential, limitations, and future perspectives of CAR-NK therapy in treating solid tumors, with a focus on its ongoing development and clinical translation.

国家自然科学基金优青项目（No. 82222054）；国家重点研发计划“常见多发病防治研究”重点专项项目（No. 2023YFC2505900）