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基于自然杀伤细胞的癌症免疫疗法

NK Cell-Based Immunotherapies in Cancer.

作者信息

Shin Min Hwa, Kim Junghee, Lim Siyoung A, Kim Jungwon, Kim Seong-Jin, Lee Kyung-Mi

机构信息

Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul 02841, Korea.

Precision Medicine Research Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Korea.

出版信息

Immune Netw. 2020 Mar 9;20(2):e14. doi: 10.4110/in.2020.20.e14. eCollection 2020 Apr.

Abstract

With the development of technologies that can transform immune cells into therapeutic modalities, immunotherapy has remarkably changed the current paradigm of cancer treatment in recent years. NK cells are components of the innate immune system that act as key regulators and exhibit a potent tumor cytolytic function. Unlike T cells, NK cells exhibit tumor cytotoxicity by recognizing non-self, without deliberate immunization or activation. Currently, researchers have developed various approaches to improve the number and anti-tumor function of NK cells. These approaches include the use of cytokines and Abs to stimulate the efficacy of NK cell function, adoptive transfer of autologous or allogeneic expanded NK cells, establishment of homogeneous NK cell lines using the NK cells of patients with cancer or healthy donors, derivation of NK cells from induced pluripotent stem cells (iPSCs), and modification of NK cells with cutting-edge genetic engineering technologies to generate chimeric Ag receptor (CAR)-NK cells. Such NK cell-based immunotherapies are currently reported as being promising anti-tumor strategies that have shown enhanced functional specificity in several clinical trials investigating malignant tumors. Here, we summarize the recent advances in NK cell-based cancer immunotherapies that have focused on providing improved function through the use of the latest genetic engineering technologies. We also discuss the different types of NK cells developed for cancer immunotherapy and present the clinical trials being conducted to test their safety and efficacy.

摘要

随着能够将免疫细胞转化为治疗方式的技术的发展,近年来免疫疗法显著改变了当前癌症治疗的模式。自然杀伤(NK)细胞是先天免疫系统的组成部分,作为关键调节因子,具有强大的肿瘤细胞溶解功能。与T细胞不同,NK细胞通过识别非自身物质表现出肿瘤细胞毒性,无需特意免疫或激活。目前,研究人员已开发出多种方法来增加NK细胞数量并提高其抗肿瘤功能。这些方法包括使用细胞因子和抗体来刺激NK细胞功能的效力、自体或异体扩增NK细胞的过继性转移、利用癌症患者或健康供体的NK细胞建立同源NK细胞系、从诱导多能干细胞(iPSC)中衍生NK细胞,以及使用前沿基因工程技术改造NK细胞以生成嵌合抗原受体(CAR)-NK细胞。目前有报道称,这种基于NK细胞的免疫疗法是很有前景的抗肿瘤策略,在几项针对恶性肿瘤的临床试验中已显示出增强的功能特异性。在此,我们总结了基于NK细胞的癌症免疫疗法的最新进展,这些进展主要集中在通过使用最新基因工程技术来提供改善的功能。我们还讨论了为癌症免疫疗法开发的不同类型的NK细胞,并介绍了正在进行的测试其安全性和疗效的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f5/7192832/916cf5616bdb/in-20-e14-g001.jpg

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