Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer.
Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer.
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DOI：
10.3389/fimmu.2018.00283
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发表时间：
2018
影响因子：
7.3
通讯作者：
Rezvani K
中科院分区：
文献类型：
--
作者：
Mehta RS;Rezvani K
过继细胞疗法已经成为对常规药物耐药的晚期癌症的一种有效治疗方法。最值得注意的是，在接受自体CD19重定向嵌合抗原受体(CAR)T细胞治疗B淋巴系恶性肿瘤的患者中看到了显著的反应；然而，为每个患者生成自体产品在后勤上是繁琐的，并限制了广泛的临床应用。储存的同种异体产品有可能克服这些限制，但同种异体T细胞(即使人类白细胞抗原匹配)携带移植物抗宿主病(GVHD)的主要风险。自然杀伤细胞(NK细胞)是骨髓来源的先天淋巴细胞，可直接清除肿瘤，其活性受激活和抑制受体以及IL-15、IL-12和IL-18等细胞因子信号的整合。NK细胞不会引起移植物抗宿主病(GVHD)或其他同种异体免疫或自身免疫毒性反应，因此，可以提供一种潜在的同种异体“现成”细胞疗法，在不引起潜在的致命性同种异体反应(如移植物抗宿主病)的情况下，介导主要的抗肿瘤作用。鉴于NK细胞的多种独特优势，研究人员现在正在探索使用CAR工程的NK细胞来治疗各种血液和非血液系统恶性肿瘤。在此，我们回顾了有关CAR-NK细胞发展的临床前数据、优缺点以及目前临床应用的障碍。
Adoptive cell therapy has emerged as a powerful treatment for advanced cancers resistant to conventional agents. Most notable are the remarkable responses seen in patients receiving autologous CD19-redirected chimeric antigen receptor (CAR) T cells for the treatment of B lymphoid malignancies; however, the generation of autologous products for each patient is logistically cumbersome and has restricted widespread clinical use. A banked allogeneic product has the potential to overcome these limitations, yet allogeneic T-cells (even if human leukocyte antigen-matched) carry a major risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are bone marrow-derived innate lymphocytes that can eliminate tumors directly, with their activity governed by the integration of signals from activating and inhibitory receptors and from cytokines including IL-15, IL-12, and IL-18. NK cells do not cause GVHD or other alloimmune or autoimmune toxicities and thus, can provide a potential source of allogeneic “off-the-shelf” cellular therapy, mediating major anti-tumor effects without inducing potentially lethal alloreactivity such as GVHD. Given the multiple unique advantages of NK cells, researchers are now exploring the use of CAR-engineered NK cells for the treatment of various hematological and non-hematological malignancies. Herein, we review preclinical data on the development of CAR-NK cells, advantages, disadvantages, and current obstacles to their clinical use.