Bollino Dominique, Webb Tonya J
Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, Md.
Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, Md.
Transl Res. 2017 Sep;187:32-43. doi: 10.1016/j.trsl.2017.06.003. Epub 2017 Jun 9.
Natural killer (NK) cells of the innate immune system and natural killer T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies. Most of the CAR studies have focused on their expression in T cells; however, the functional heterogeneity of CAR T cells limits their therapeutic potential and is associated with toxicity. CAR-modified NK and NKT cells are becoming more prevalent because they provide a method to direct these cells more specifically to target cancer cells, with less risk of adverse effects. This review will outline current NK and NKT cell CAR constructs and how they compare to conventional CAR T cells, and discuss future modifications that can be explored to advance adoptive cell transfer of NK and NKT cells.
天然免疫系统的自然杀伤（NK）细胞和在先天性及适应性免疫反应中均发挥作用的自然杀伤T（NKT）细胞，是在功能和表型上具有相似性的独特淋巴细胞亚群。这两种细胞类型都能对肿瘤细胞的出现迅速做出反应，并参与免疫监视和抗肿瘤免疫反应。这激发了人们对基于NK和NKT细胞操控开发新型癌症治疗方法的兴趣。嵌合抗原受体（CAR）是通过将单克隆抗体或其他配体的抗原结合区域与细胞内信号结构域融合而产生的，它可以增强淋巴细胞对多种恶性肿瘤的靶向性和激活作用。大多数CAR研究都集中在它们在T细胞中的表达；然而，CAR T细胞的功能异质性限制了它们的治疗潜力，并与毒性相关。CAR修饰的NK和NKT细胞正变得越来越普遍，因为它们提供了一种更特异性地引导这些细胞靶向癌细胞的方法，且不良反应风险较低。本综述将概述当前NK和NKT细胞的CAR构建体以及它们与传统CAR T细胞的比较，并讨论为推进NK和NKT细胞的过继性细胞转移而可探索的未来改进方法。
