Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China.
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
J Transl Med. 2022 May 23;20(1):240. doi: 10.1186/s12967-022-03437-0.
As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK cells can rapidly kill multiple adjacent cancer cells through non-MHC-restrictive effects. Although tumors may develop multiple resistance mechanisms to endogenous NK cell attack, in vitro activation, expansion, and genetic modification of NK cells can greatly enhance their anti-tumor activity and give them the ability to overcome drug resistance. Some of these approaches have been translated into clinical applications, and clinical trials of NK cell infusion in patients with hematological malignancies and solid tumors have thus far yielded many encouraging clinical results. CAR-T cells have exhibited great success in treating hematological malignancies, but their drawbacks include high manufacturing costs and potentially fatal toxicity, such as cytokine release syndrome. To overcome these issues, CAR-NK cells were generated through genetic engineering and demonstrated significant clinical responses and lower adverse effects compared with CAR-T cell therapy. In this review, we summarize recent advances in NK cell immunotherapy, focusing on NK cell biology and function, the types of NK cell therapy, and clinical trials and future perspectives on NK cell therapy.
作为细胞免疫治疗的一种有前途的替代平台,自然杀伤细胞 (NK) 最近作为一种重要的固有免疫调节细胞引起了人们的关注。NK 细胞可以通过非 MHC 限制作用快速杀死多个相邻的癌细胞。尽管肿瘤可能会发展出多种抵抗内源性 NK 细胞攻击的机制,但在体外激活、扩增和遗传修饰 NK 细胞可以大大增强其抗肿瘤活性,并使它们具有克服耐药性的能力。其中一些方法已经转化为临床应用,目前 NK 细胞输注治疗血液系统恶性肿瘤和实体瘤的临床试验已经取得了许多令人鼓舞的临床结果。嵌合抗原受体 T 细胞 (CAR-T 细胞) 在治疗血液系统恶性肿瘤方面取得了巨大成功,但它们存在制造成本高和潜在致命毒性(如细胞因子释放综合征)等缺点。为了克服这些问题,通过基因工程产生了嵌合抗原受体自然杀伤细胞 (CAR-NK 细胞),与 CAR-T 细胞治疗相比,其具有显著的临床反应和更低的不良反应。在这篇综述中,我们总结了 NK 细胞免疫治疗的最新进展,重点介绍了 NK 细胞的生物学和功能、NK 细胞治疗的类型以及 NK 细胞治疗的临床试验和未来展望。