Zhou Zhaokai, Chen Yifeng, Ba Yuhao, Xu Hui, Zuo Anning, Liu Shutong, Zhang Yuyuan, Weng Siyuan, Ren Yuqing, Luo Peng, Cheng Quan, Zuo Lulu, Zhu Shanshan, Zhou Xing, Zhang Chuhan, Chen Yukang, Han Xinwei, Pan Teng, Liu Zaoqu
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Cell Prolif. 2025 Apr;58(4):e13791. doi: 10.1111/cpr.13791. Epub 2024 Dec 27.
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.
癌症免疫疗法的最新进展凸显了自然杀伤（NK）细胞的潜力，特别是嵌合抗原受体（CAR）转导的NK细胞。这些在先天免疫中起关键作用的细胞，无需预先致敏或识别肽抗原，就能对癌细胞和病原体迅速产生强烈反应。尽管NK细胞基因改造技术不断发展，但病毒转导方法仍然效率低下且充满风险，常常导致细胞毒性结果以及插入诱变的可能性。因此，为克服NK细胞工程中的这些挑战，非病毒转染技术的开发激增。用于生成CAR-NK细胞的非病毒方法正变得越来越重要。诸如胞啃作用、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）基因编辑和转座子等前沿技术，不仅提高了CAR-NK细胞工程的效率和安全性，还为新的治疗可能性开辟了新途径。此外，将已在CAR T细胞疗法中取得成功的技术引入CAR-NK模式，具有进一步推进的巨大潜力。在这篇综述中，我们概述了NK细胞在癌症免疫疗法中的潜力，以及用于工程化NK细胞的非病毒转染技术。
