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泌尿系统肿瘤中的 NK 细胞与 CAR-NK 细胞治疗:进展、来自 CAR-T 的机制启示及未来方向

英文原题:Natural killer and CAR-NK cell therapies in urological cancers: Progress, mechanistic lessons from CAR-T, and future directions.

PubMed 2026/02/13(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

研究概要

我们得出结论:尽管 CAR-NK 疗法是治疗这些癌症的一种有前景的「即用型」手段,但其在实体瘤中的成功取决于下一代设计,这些设计需解决体内持久性、高效肿瘤归巢以及抵抗局部代谢与免疫抑制压力等关键挑战。

中文摘要

本综述总结自然杀伤(NK)和嵌合抗原受体NK(CAR-NK)细胞疗法治疗泌尿系统肿瘤(包括肾细胞癌、膀胱癌和前列腺癌)的现有进展、挑战及未来方向。文章介绍NK细胞独特生物学特征,如“缺失自身”识别及内在抗体依赖性细胞毒作用(ADCC),这些特性可能使其相较CAR-T具有安全性和疗效优势,包括重度细胞因子释放综合征和移植物抗宿主病风险较低。分析涵盖传统NK细胞策略、CAR-NK平台工程化和“装甲化”以克服免疫抑制性肿瘤微环境,以及针对CAIX、CD70、PSMA和nectin-4等抗原治疗不同泌尿系统恶性肿瘤的临床前和早期临床进展。综述认为,CAR-NK有望成为治疗这些癌症的“现货型”方式,但其实体瘤疗效取决于新一代设计能否解决体内持续性、有效肿瘤归巢,以及抵抗局部代谢和免疫抑制压力等关键问题。

展开英文摘要原文

This review aims to synthesize the current progress, challenges, and future directions of Natural Killer (NK) and Chimeric Antigen Receptor-NK (CAR-NK) cell therapies for urological cancers, including renal cell carcinoma, bladder cancer, and prostate cancer. We detail the unique biology of NK cells, such as 'missing-self' recognition and intrinsic antibody-dependent cellular cytotoxicity (ADCC), which offer potential safety and efficacy advantages over CAR-T cells, including a lower risk of severe cytokine release syndrome and graft-versus-host disease. The analysis covers conventional NK-based strategies, the engineering and 'armouring' of CAR-NK platforms to overcome the immunosuppressive tumour microenvironment, and preclinical and early clinical advances with target antigens like CAIX, CD70, PSMA, and nectin-4 across different urological malignancies. We conclude that while CAR-NK therapy represents a promising 'off-the-shelf' modality for these cancers, its success in solid tumours hinges on next-generation designs that solve critical challenges of in vivo persistence, efficient tumour homing, and resistance to local metabolic and immunosuppressive pressures.

论文信息

作者
Zhou Z、Zhao K、Xiao X、Yang W、Miao Y、Wu T、Kong X、Tao Y
第一作者单位
Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, China; Institute of Urology, Gansu Province Clinical Research Center for Urinary System Diseases, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.China
通讯作者单位
Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, China; Institute of Urology, Gansu Province Clinical Research Center for Urinary System Diseases, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China. Electronic address: dzl19780829@163.com.China
文献类型
综述
期刊
Critical reviews in oncology/hematology2026 May
原文标识
PubMed 41692037 · DOI 10.1016/j.critrevonc.2026.105208