Hermanson David L, Kaufman Dan S
Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota , Minneapolis, MN , USA ; Stem Cell Institute, University of Minnesota , Minneapolis, MN , USA.
Front Immunol. 2015 Apr 28;6:195. doi: 10.3389/fimmu.2015.00195. eCollection 2015.
Natural killer (NK) cells represent an attractive lymphocyte population for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization and without need for human leukocyte antigens-matching. Chimeric antigen receptors (CARs) are able to enhance lymphocyte targeting and activation toward diverse malignancies. CARs consist of an external recognition domain (typically a small chain variable fragment) directed at a specific tumor antigen that is linked with one or more intracellular signaling domains that mediate lymphocyte activation. Most CAR studies have focused on their expression in T cells. However, use of CARs in NK cells is starting to gain traction because they provide a method to redirect these cells more specifically to target refractory cancers. CAR-mediated anti-tumor activity has been demonstrated using NK cell lines, as well as NK cells isolated from peripheral blood, and NK cells produced from human pluripotent stem cells. This review will outline the CAR constructs that have been reported in NK cells with a focus on comparing the use of different signaling domains in combination with other co-activating domains.
自然杀伤（NK）细胞因其能够在无需预先致敏且无需人类白细胞抗原匹配的情况下裂解肿瘤靶标，而成为癌症免疫治疗中颇具吸引力的淋巴细胞群体。嵌合抗原受体（CAR）能够增强淋巴细胞对多种恶性肿瘤的靶向作用和激活作用。CAR由一个针对特定肿瘤抗原的外部识别域（通常是一个小链可变片段）组成，该识别域与一个或多个介导淋巴细胞激活的细胞内信号域相连。大多数CAR研究都集中在其在T细胞中的表达。然而，在NK细胞中使用CAR正开始受到关注，因为它们提供了一种将这些细胞更特异性地重定向至难治性癌症靶标的方法。使用NK细胞系、从外周血分离的NK细胞以及由人类多能干细胞产生的NK细胞，均已证明CAR介导的抗肿瘤活性。本综述将概述已在NK细胞中报道的CAR构建体，重点是比较不同信号域与其他共激活域组合的使用情况。
