NK细胞免疫治疗恶性肿瘤的研究进展

doi:10.3969/j.issn.1671-2587.2024.02.017

临床输血与检验 ›› 2024, Vol. 26 ›› Issue (2): 267-273.DOI: 10.3969/j.issn.1671-2587.2024.02.017

NK细胞免疫治疗恶性肿瘤的研究进展

曹腾宇^1,2, 孙莉萍², 于洋²

¹解放军医学院,北京 100853;
²中国人民解放军总医院第一医学中心输血医学科,北京 100853

收稿日期:2024-01-09 出版日期:2024-04-20 发布日期:2024-04-23
通讯作者: 于洋, 主要从事单采治疗、野战输血及智能化输血辅助决策系统研究,（E-mail）yuyangpla301@163.com。共同通信作者：孙莉萍,主要从事输血医学基础研究,（E-mail）sunlp2012@sina.com。
作者简介:曹腾宇,主要从事输血与免疫方面研究,（E-mail）ava_qswcblbq@163.com。

Current Trends in NK Cell Immunotherapy for Malignant Tumors

CAO Tengyu^1,2, SUN Liping², YU Yang²

¹Medical School of Chinese PLA, Beijing 100853;
²Department of Tranfusion Medicine,the First Medical Center,Chinese PLA General Hospital, Beijing 100853

Received:2024-01-09 Online:2024-04-20 Published:2024-04-23

摘要/Abstract

摘要： 细胞免疫治疗是针对自身免疫细胞能力低下的恶性肿瘤患者进行的一种新型补充疗法,包括基于T细胞的嵌合抗原受体T细胞（CAR-T）疗法、肿瘤浸润淋巴细胞（TILs）疗法,基于NK细胞的嵌合抗原受体NK细胞（CAR-NK）疗法和自体细胞免疫疗法（CIK）,还有基于其他免疫细胞如单核吞噬细胞,包括树突状细胞和巨噬细胞的输注治疗。其中,自然杀伤细胞（nature killer cell,NK细胞）作为机体天然免疫的重要细胞,在机体抗肿瘤、抗病毒感染、免疫调节中发挥着重要作用。它可以像T细胞一样通过工程化改造后靶向治疗肿瘤,还能够进行同种异体来源的NK细胞输注治疗,弥补了T细胞自体来源受限和异体免疫排斥的缺点。研究证实,输注异体NK细胞的患者不会发生严重的移植物抗宿主病（graft versus host disease,GVHD）。NK细胞不仅扩大了用于细胞免疫治疗的细胞种类,还为形成较低成本的细胞免疫治疗产品提供了广阔应用前景。但是目前仍存在NK细胞质量不稳定,制备流程缺乏统一质量标准等问题,虽有部分NK细胞免疫治疗产品已经获得了美国食品药品监督管理局（Food and Drug Administration,FDA））或国家药品监督管理局（National Medical Products Administration,NMPA）的批准,但仍然没有明确公开的NK细胞免疫治疗产品的规范生产体系。本文从NK细胞独特的免疫调节作用机制出发,综合近年研究者利用NK细胞在恶性肿瘤治疗上应用的治疗策略和临床前研究及临床试验的最新进展,最终落脚于NK细胞的体外扩增办法及活性功能维持的研究进展上,表明NK细胞有望形成质量统一的细胞免疫治疗产品。

关键词: NK细胞, 细胞免疫治疗, 异体过继输入, 体外扩增, CAR-NK

Abstract: Cellular immunotherapies, new complementary therapies for tumor patients, are aimed at malignant tumors with low ability of autoimmune cells, including T cell-based chimeric antigen receptor T cell (CAR-T) therapy, tumor infiltrating lymphocytes (TILs) therapy, NK cell-based chimeric antigen receptor NK cell (CAR-NK) therapy, and autologous cell immunotherapy (CIK), as well as infusion therapies based on other immune cells such as mononuclear phagocytes like dendritic cells and macrophages. Among them, nature killer cells (NK cells), important to the body's natural immunity, matter greatly in anti-tumor, antiviral infection and immune regulation. Like T cells, it can be engineered to target tumor treatment, and can also be transfused with allogeneic NK cells, making up for the shortcomings of limited T cell source and allogeneic immune rejection. No evidence shows that patients tansfused with allogeneic NK cells may develop severe Graft Versus Host Disease (GVHD). NK cells not only expand the types of cells used in cellular immunotherapy, but also provide a broad application prospect for the formation of low-cost cellular immunotherapy products. However, there are still problems such as unstable quality of NK cells and lack of unified quality standards in the preparation process. Although some NK cell immunotherapy products have been approved by the Food and Drug Administration (FDA) or the National Medical Products Administration (NMPA), there is still no clear and publicly available standardized production system for NK cell immunotherapy products. Starting from the unique immunomodulatory mechanism of NK cells, this paper summarizes the therapeutic strategies applied by researchers in the treatment of malignant tumors in recent years and the latest progress of preclinical studies and clinical trials, and finally focuses on the research progress of in vitro expansion methods and maintenance of active function of NK cells, indicating that NK cells promise to be a unified quality of cellular immunotherapy products.

Key words: NK cells, Cell immunotherapy, Allogeneic adoptive input, In vitro amplification, CAR-NK

曹腾宇, 孙莉萍, 于洋. NK细胞免疫治疗恶性肿瘤的研究进展[J]. 临床输血与检验, 2024, 26(2): 267-273.

CAO Tengyu, SUN Liping, YU Yang. Current Trends in NK Cell Immunotherapy for Malignant Tumors[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(2): 267-273.

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NK细胞免疫治疗恶性肿瘤的研究进展

Current Trends in NK Cell Immunotherapy for Malignant Tumors

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