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用于癌症治疗的工程化 NK 细胞

英文原题:Engineered natural killer cells for cancer therapy.

PubMed 2025/10/23(内容时间) Cancer Cell Q1 · IF 56.1(JCR 2025)

研究概要

这些转化创新共同界定了下一代 NK 细胞治疗的发展轨迹及其融入更广泛癌症免疫治疗格局的路径。

中文摘要

异体自然杀伤(NK)细胞免疫疗法正成为一种有前景、可规模化生产的现货型平台,用于治疗复发和难治性癌症。早期临床试验显示,嵌合抗原受体(CAR)NK细胞治疗既往接受多线治疗的淋巴系统恶性肿瘤患者具有显著安全性和令人鼓舞的疗效。目前研究正将这些疗法拓展至实体瘤;转化研究越来越多地采用精准基因编辑,以增强效应功能、延长细胞持续存在时间,并提高其抵抗免疫抑制性肿瘤微环境的能力。本综述总结早期临床试验结果,并讨论增强NK细胞效能的新兴合成生物学和工程化策略。我们还介绍高通量发现平台的进展,这些平台已鉴定出可操作的基因靶点,用于重编程NK细胞,并为设计多重工程化CAR-NK细胞、克服实体瘤治疗挑战提供路径。这些转化创新共同勾勒了新一代NK细胞疗法的发展轨迹,以及其融入更广泛癌症免疫治疗领域的前景。

展开英文摘要原文

Allogeneic natural killer (NK) cell immunotherapy is emerging as a promising and scalable, off-the-shelf platform for treating relapsed and refractory cancers. Early-phase clinical trials have demonstrated remarkable safety and encouraging therapeutic efficacy of chimeric antigen receptor (CAR)-NK cells in heavily pretreated patients with lymphoid malignancies. Current efforts are expanding these therapies to solid tumors, with translational research increasingly leveraging precision gene editing to enhance effector function, persistence, and resistance to the immunosuppressive tumor microenvironment. In this review, we summarize findings from early-phase clinical trials and discuss emerging synthetic biology and engineering approaches to improve NK cell potency. We also highlight advances in high-throughput discovery platforms that have identified actionable gene targets for NK cell reprogramming, offering a path to design multi-engineered CAR-NK cells to overcome the challenges of solid tumors. Together, these translational innovations define the trajectory of next-generation NK cell therapies and their integration into the broader cancer immunotherapy landscape.

论文信息

作者
Biederstädt A、Rezvani K
第一作者单位
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Medicine III: Hematology & Oncology, School of Medicine, Technical University of Munich, Munich, Germany.United States
通讯作者单位
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: krezvani@mdanderson.org.United States
文献类型
综述
期刊
Cancer cell2025 Nov 10
原文标识
PubMed 41135520 · DOI 10.1016/j.ccell.2025.09.013