Department of Hematology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Institute of Clinical Medicine College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Immunol. 2022 Jun 10;13:927153. doi: 10.3389/fimmu.2022.927153. eCollection 2022.
Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-related coagulopathy. In addition, due to antigen escape, the limited CAR-T cell persistence, and immunosuppressive tumor microenvironment, a considerable proportion of patients relapse after CAR-T cell therapy. Thus, in this review, we focus on the progress and challenges of CAR-T cell therapy in hematological malignancies, such as attractive therapeutic targets, CAR-T related toxicities, and resistance to CAR-T cell therapy, and provide some practical recommendations.
嵌合抗原受体 T(CAR-T)细胞疗法代表了癌症治疗的重大突破,它在血液系统恶性肿瘤中取得了前所未有的成功,尤其是在复发/难治性(R/R)B 细胞恶性肿瘤中。目前,CD19 和 BCMA 是 CAR-T 细胞疗法中最常见的靶点,并且正在探索许多新的治疗靶点。然而,与 CAR-T 细胞疗法相关的不良事件可能很严重,甚至危及生命,如细胞因子释放综合征(CRS)、CAR-T 细胞相关脑病综合征(CRES)、感染、血细胞减少症和 CRS 相关的凝血障碍。此外,由于抗原逃逸、CAR-T 细胞持续时间有限和免疫抑制性肿瘤微环境,相当一部分患者在 CAR-T 细胞治疗后复发。因此,在这篇综述中,我们重点关注 CAR-T 细胞疗法在血液系统恶性肿瘤中的进展和挑战,如有吸引力的治疗靶点、CAR-T 相关毒性和对 CAR-T 细胞疗法的耐药性,并提供一些实用建议。