Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center, Chengdu, 610041, China.
Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center, Chengdu, 610041, China.
Cancer Lett. 2023 Jan 28;553:215949. doi: 10.1016/j.canlet.2022.215949. Epub 2022 Oct 8.
Multiple myeloma (MM) remains an incurable hematologic malignancy, despite the development of numerous innovative therapies during the past two decades. Immunotherapies are changing the treatment paradigm of MM and have improved the overall response and survival of patients with relapsed/refractory (RR) MM. B cell maturation antigen (BCMA), selectively expressed in normal and malignant plasma cells, has been targeted by several immunotherapeutic modalities. Chimeric antigen receptor (CAR) T cells, the breakthrough in cancer immunotherapy, have revolutionized the treatment of B cell malignancies and remarkably improved the prognosis of RRMM. BCMA-targeting CAR T cell therapy is the most developed CAR T cell therapy for MM, and the US Food and Drug Administration has already approved idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) for MM. However, the development of novel BCMA-targeting CAR T cell therapies remains in progress. This review focuses on BCMA-targeting CAR T cell therapy, covering all stages of investigational progress, including the innovative preclinical studies, the initial phase I clinical trials, and the more developed phase II clinical trials. It also discusses possible measures to improve the efficacy and safety of this therapy.
多发性骨髓瘤(MM)仍然是一种无法治愈的血液恶性肿瘤,尽管在过去二十年中开发了许多创新疗法。免疫疗法正在改变 MM 的治疗模式,并改善了复发/难治性(RR)MM 患者的总体反应和生存。B 细胞成熟抗原(BCMA)在正常和恶性浆细胞中选择性表达,已被几种免疫治疗方法靶向。嵌合抗原受体(CAR)T 细胞是癌症免疫治疗的突破,彻底改变了 B 细胞恶性肿瘤的治疗方法,并显著改善了 RRMM 的预后。BCMA 靶向 CAR T 细胞疗法是最成熟的 MM CAR T 细胞疗法,美国食品和药物管理局已经批准 idecabtagene vicleucel(Ide-cel)和 ciltacabtagene autoleucel(Cilta-cel)用于 MM。然而,新型 BCMA 靶向 CAR T 细胞疗法的开发仍在进行中。本综述重点介绍了 BCMA 靶向 CAR T 细胞疗法,涵盖了研究进展的所有阶段,包括创新的临床前研究、初步的 I 期临床试验以及更成熟的 II 期临床试验。它还讨论了提高这种疗法疗效和安全性的可能措施。