提高CAR-T细胞免疫疗法有效性和安全性的新策略

New Strategies to Improve Efficiency and Safety of Chimeric Antigen Receptor T Cell(CAR-T) Immunotherapy

近年来,嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)免疫疗法发展迅速,尤其是在急性B系淋巴细胞白血病和非霍奇金淋巴瘤的治疗上取得了显著疗效。虽然CAR-T细胞免疫疗法是一种非常有前景的新型肿瘤免疫治疗方式,但是其应用仍然存在许多局限性:一方面,CAR-T细胞免疫疗法治疗实体瘤的疗效不佳;另一方面,CAR-T细胞免疫疗法在治疗过程中会出现细胞因子风暴等严重的并发症。该文主要从增强T细胞的定向运输和浸润、减缓或消除效应T细胞的衰竭以及拮抗肿瘤的免疫抑制微环境等方面概述提高CAR-T细胞治疗有效性的新策略,以及通过增强CAR-T识别并杀伤肿瘤细胞的特异性和更有效地调控T细胞活性的启动和关闭等新策略,提高CAR-T细胞治疗的安全性。

Chimeric antigen receptor T cell(CAR-T) immunotherapy has developed rapidly in recent years, especially in the treatment of acute B lymphoblastic leukemia and non-Hodgkin lymphoma.However, there are some limitations for CAR-T immunotherapy: it may not produce ideal curative effect in solid tumors;and serious complications, such as cytokine release syndrome, may occur during the treatment. New strategies to improve efficacy and safety of CAR-T immunotherapy are summaried in this article, including enhancing directional transportation and infiltration of T cells, relieving or eliminating exhaustion of effector T cells, and antagonizing the immuno-suppressive microenvironment of tumors;and the strategies of improving the specificity of CAR-T cells, "turning on" and "turning off " T cells activation are also discussed.