Park Joo Dong, Shin Ha Eun, An Yeon Su, Jang Hye Jung, Park Juwon, Kim Se-Na, Park Chun Gwon, Park Wooram
Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Korea.
Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School Medicine, University of Hawai'i at Manoa, Honolulu, USA.
Ann Lab Med. 2025 Mar 1;45(2):146-159. doi: 10.3343/alm.2024.0380. Epub 2025 Jan 8.
Natural killer (NK) cells are pivotal innate immune system components that exhibit spontaneous cytolytic activity against abnormal cells, such as infected and tumor cells. NK cells have shown significant promise in adoptive cell therapy because of their favorable safety profiles and minimal toxicity in clinical settings. Despite their advantages, the therapeutic application of unmodified NK cells faces challenges, including limited in vivo persistence, particularly in the immunosuppressive tumor microenvironment. Recent advances in genetic engineering have enhanced the therapeutic potential of NK cells by addressing these limitations and improving their therapeutic efficacy. In this review, we have described various methodologies for the genetic modification of NK cells, including viral vectors, electroporation, and nanoparticle-based approaches. The ongoing research on nanomaterialbased approaches highlights their potential to overcome current limitations in NK cell therapy, paving the way for advanced cancer therapy and improved clinical outcomes. In this review, we also emphasize the potential of engineered NK cells in cancer immunotherapy and other clinical applications, highlighting the expanding scope of NK cell-based treatments and the critical role of innovative genetic engineering techniques.
自然杀伤（NK）细胞是先天性免疫系统的关键组成部分，对异常细胞（如受感染细胞和肿瘤细胞）具有自发的细胞溶解活性。由于其良好的安全性和在临床环境中的低毒性，NK细胞在过继性细胞治疗中显示出巨大的前景。尽管具有这些优势，但未经修饰的NK细胞的治疗应用仍面临挑战，包括在体内的持久性有限，尤其是在免疫抑制性肿瘤微环境中。基因工程的最新进展通过解决这些局限性并提高其治疗效果，增强了NK细胞的治疗潜力。在这篇综述中，我们描述了NK细胞基因改造的各种方法，包括病毒载体、电穿孔和基于纳米颗粒的方法。正在进行的基于纳米材料方法的研究突出了它们克服NK细胞治疗当前局限性的潜力，为先进的癌症治疗和改善临床结果铺平了道路。在这篇综述中，我们还强调了工程化NK细胞在癌症免疫治疗和其他临床应用中的潜力，突出了基于NK细胞治疗范围的不断扩大以及创新基因工程技术的关键作用。
