CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma.
BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma.
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多发性骨髓瘤(MM)仍然是一种无法治愈的血液系统恶性肿瘤,尽管在过去二十年中开发了众多创新疗法。免疫疗法正在改变MM的治疗范式,并改善了复发/难治性(RR)MM患者的总体缓解率和生存期。B细胞成熟抗原(BCMA)选择性表达于正常和恶性浆细胞,已成为多种免疫治疗方式的靶点。嵌合抗原受体(CAR)T细胞是癌症免疫治疗的突破性进展,彻底改变了B细胞恶性肿瘤的治疗,并显著改善了RRMM的预后。靶向BCMA的CAR-T 细胞疗法是MM领域最成熟的CAR-T 细胞疗法,美国食品药品监督管理局已批准idecabtagene vicleucel(Ide-cel)和ciltacabtagene autoleucel(Cilta-cel)用于MM。
然而,新型靶向BCMA的CAR-T 细胞疗法的开发仍在进行中。本综述聚焦于靶向BCMA的CAR-T 细胞疗法,涵盖研究进展的各个阶段,包括创新的临床前研究、初步的I期临床试验以及更为成熟的II期临床试验。同时讨论了提高该疗法疗效和安全性的可能措施。
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.
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