Kexin Wang, Linqin Wang, Yiyun Wang, Lu Xiao, Jieping Wei, Yongxian Hu, Dongrui Wang, He Huang
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引用次数: 0
Abstract
The last decade has seen rapid development in the field of cellular immunotherapy, particularly in regard to chimeric antigen receptor (CAR)-modified T cells. However, challenges, such as severe treatment-related toxicities and inconsistent quality of autologous products, have hindered the broader use of CAR-T cell therapy, highlighting the need to explore alternative immune cells for cancer targeting. In this regard, natural killer (NK) cells have been extensively studied in cellular immunotherapy and were found to exert cytotoxic effects without being restricted by human leukocyte antigen and have a lower risk of causing graft-versus-host disease; making them favorable for the development of readily available "off-the-shelf" products. Clinical trials utilizing unedited NK cells or reprogrammed NK cells have shown early signs of their effectiveness against tumors. However, limitations, including limited in vivo persistence and expansion potential, remained. To enhance the antitumor function of NK cells, advanced gene-editing technologies and combination approaches have been explored. In this review, we summarize current clinical trials of antitumor NK cell therapy, provide an overview of innovative strategies for reprogramming NK cells, which include improvements in persistence, cytotoxicity, trafficking and the ability to counteract the immunosuppressive tumor microenvironment, and also discuss some potential combination therapies.
过去十年,细胞免疫疗法领域发展迅速,尤其是嵌合抗原受体(CAR)修饰的 T 细胞。然而,与治疗相关的严重毒性和自体产品的质量不稳定等挑战阻碍了 CAR-T 细胞疗法的广泛应用,凸显了探索其他免疫细胞用于癌症靶向治疗的必要性。在这方面,自然杀伤(NK)细胞在细胞免疫疗法中得到了广泛的研究,并发现其细胞毒性作用不受人类白细胞抗原(HLA)的限制,而且引起移植物抗宿主病(GvHD)的风险较低;因此有利于开发现成的 "现货 "产品。利用未经编辑的 NK 细胞或重新编程的 NK 细胞进行的临床试验已显示出它们对肿瘤有效的早期迹象。然而,其局限性依然存在,包括体内持久性和扩增潜力有限。为了增强 NK 细胞的抗肿瘤功能,人们探索了先进的基因编辑技术和组合方法。在这篇综述中,我们总结了目前抗肿瘤 NK 细胞疗法的临床试验,概述了对 NK 细胞进行重编程的创新策略,其中包括改善持久性、细胞毒性、迁移和对抗免疫抑制性肿瘤微环境(TME)的能力,还讨论了一些潜在的联合疗法。
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.