Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russian Federation.
Kite Pharma/Gilead Sciences, Emeryville, CA, United States.
Curr Pharm Des. 2018;24(24):2810-2824. doi: 10.2174/1381612824666180829113013.
Natural Killer (NK) cells belong to a unique subtype of lymphocytes with a great potential for cancer immunotherapy due to their ability to rapidly recognize and efficiently kill tumor cells. Their anti-cancer potential can be further increased by genetic and non-genetic modifications. However, the attempts of genetic improvements of NK cells over the past 20 years have been hampered by the difficulties of gene delivery into this cell type, thus preventing researchers from producing clinically relevant numbers of viable and biologically active NK cells. Currently, several successful approaches to genetic modification of NK cells have been described, and clinically applicable cell therapy products have been characterized. Now that we understand much better the ways of NK cell optimization to enhance their tumor regression-inducing capabilities, novel approaches to engineering NK surface receptors are being developed. In this review, we focus on the advantages and perspectives of various approaches to modification of NK cells. Positive results of several preclinical studies are described, demonstrating that genetically modified NK cells can be comparable to therapeutic T cells in their efficiency of recognizing and destroying tumor targets. Moreover, using allogenic NK cells to treat a number of cancer types might have even wider and eager clinical adoption than cytotoxic T cells due to a much decreased risk of graft versus host reaction inherent in NK cell-based immunotherapeutic products.
自然杀伤 (NK) 细胞属于一种独特的淋巴细胞亚群，具有很大的癌症免疫治疗潜力，因为它们能够快速识别并有效地杀死肿瘤细胞。通过遗传和非遗传修饰可以进一步提高其抗癌潜力。然而，在过去 20 年中，对 NK 细胞进行遗传改良的尝试受到了将基因递送到这种细胞类型的困难的阻碍，从而阻止了研究人员产生具有临床相关性的、存活的和具有生物活性的 NK 细胞。目前，已经描述了几种成功的 NK 细胞遗传修饰方法，并对临床适用的细胞治疗产品进行了表征。既然我们对优化 NK 细胞以增强其肿瘤消退诱导能力的方法有了更好的了解，那么新型的 NK 细胞表面受体工程方法也正在开发中。在这篇综述中，我们重点介绍了修饰 NK 细胞的各种方法的优缺点和前景。描述了几项临床前研究的积极结果，证明了经过遗传修饰的 NK 细胞在识别和破坏肿瘤靶标方面的效率可以与治疗性 T 细胞相媲美。此外，由于基于 NK 细胞的免疫治疗产品固有地降低了移植物抗宿主反应的风险，因此使用同种异体 NK 细胞治疗多种癌症类型可能比细胞毒性 T 细胞具有更广泛和迫切的临床应用。
