Petty Amy J, Heyman Benjamin, Yang Yiping
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Division of Regenerative Medicine, Department of Medicine, UC San Diego, La Jolla, CA 92093, USA.
Cancers (Basel). 2020 Mar 31;12(4):842. doi: 10.3390/cancers12040842.
Chimeric antigen receptors (CAR) are fusion proteins engineered from antigen recognition, signaling, and costimulatory domains that can be used to reprogram T cells to specifically target tumor cells expressing specific antigens. Current CAR-T cell technology utilizes the patient's own T cells to stably express CARs and has achieved exciting clinical success in the past few years. However, current CAR-T cell therapy still faces several challenges, including suboptimal persistence and potency, impaired trafficking to solid tumors, local immunosuppression within the tumor microenvironment and intrinsic toxicity associated with CAR-T cells. This review focuses on recent strategies to improve the clinical efficacy of CAR-T cell therapy and other exciting CAR approaches currently under investigation, including CAR natural killer (NK) and NKT cell therapies.
嵌合抗原受体（CAR）是由抗原识别、信号传导和共刺激结构域工程化构建的融合蛋白，可用于对T细胞进行重编程，以特异性靶向表达特定抗原的肿瘤细胞。目前的CAR-T细胞技术利用患者自身的T细胞来稳定表达CAR，并在过去几年中取得了令人振奋的临床成功。然而，目前的CAR-T细胞疗法仍面临若干挑战，包括持久性和效力欠佳、向实体瘤的迁移受损、肿瘤微环境内的局部免疫抑制以及与CAR-T细胞相关的内在毒性。本综述重点关注提高CAR-T细胞疗法临床疗效的近期策略以及目前正在研究的其他令人关注的CAR方法，包括CAR自然杀伤（NK）细胞疗法和NKT细胞疗法。
