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革新肿瘤免疫治疗:非病毒 CAR-NK 细胞工程的进展与前景

英文原题:Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering.

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Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering.

PubMed 2024/12/27(内容时间) Cell Prolif Q1 · IF 7.6(JCR 2025)

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中文摘要

癌症免疫治疗近期进展凸显了自然杀伤(NK)细胞,尤其是嵌合抗原受体(CAR)转导NK细胞的潜力。这些细胞是先天免疫的重要组成部分,无需预先致敏或识别肽抗原,即可快速、有力地应对癌细胞和病原体。尽管NK细胞基因修饰技术不断发展,病毒转导方法仍效率低且存在风险,常导致细胞毒性,并可能引发插入突变。因此,非病毒转染技术迅速发展,以克服NK细胞工程化的这些挑战。采用非病毒方法制备CAR-NK细胞正变得日益重要。胞啃、电穿孔、脂质纳米颗粒(LNP)递送、成簇规律间隔短回文重复序列相关蛋白9(CRISPR-Cas9)基因编辑及转座子等前沿技术,不仅提高CAR-NK工程化的效率和安全性,也为新的治疗可能性开辟了途径。此外,将已在CAR-T 细胞疗法中取得成功的技术引入CAR-NK领域,也具有巨大的进一步发展潜力。本文综述NK细胞用于癌症免疫治疗的潜力,以及工程化NK细胞的非病毒转染技术。

展开英文摘要原文

The recent advancements in cancer immunotherapy have spotlighted the potential of natural killer (NK) cells, particularly chimeric antigen receptor (CAR)-transduced NK cells. These cells, pivotal in innate immunity, offer a rapid and potent response against cancer cells and pathogens without the need for prior sensitization or recognition of peptide antigens. Although NK cell genetic modification is evolving, the viral transduction method continues to be inefficient and fraught with risks, often resulting in cytotoxic outcomes and the possibility of insertional mutagenesis.

Consequently, there has been a surge in the development of non-viral transfection technologies to overcome these challenges in NK cell engineering. Non-viral approaches for CAR-NK cell generation are becoming increasingly essential.

Cutting-edge techniques such as trogocytosis, electroporation, lipid nanoparticle (LNP) delivery, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) gene editing and transposons not only enhance the efficiency and safety of CAR-NK cell engineering but also open new avenues for novel therapeutic possibilities.

Additionally, the infusion of technologies already successful in CAR T-cell therapy into the CAR-NK paradigm holds immense potential for further advancements. In this review, we present an overview of the potential of NK cells in cancer immunotherapies, as well as non-viral transfection technologies for engineering NK cells.

论文信息

作者
Zhou Z、Chen Y、Ba Y、Xu H、Zuo A、Liu S、Zhang Y、Weng S
单位
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.China
文献类型
综述
期刊
Cell proliferation2025 Apr
原文标识
PubMed 39731215 · DOI 10.1111/cpr.13791