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多发性骨髓瘤中 BCMA 的靶向:设计、挑战与未来方向

英文原题:Targeting BCMA in multiple myeloma: designs, challenges, and future directions.

查看英文原题

Targeting BCMA in multiple myeloma: designs, challenges, and future directions.

PubMed 2025/02/01(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法已成为一种突破性的免疫疗法,在治疗B细胞恶性肿瘤方面展现出显著疗效。在多发性骨髓瘤(MM)中,B细胞成熟抗原(BCMA)已被确定为关键靶点,推动了针对这种浆细胞癌症的CAR-T 细胞疗法的开发。采用不同BCMA识别结构域的各种CAR设计已取得令人鼓舞的临床结果,促使美国食品药品监督管理局(FDA)批准了两款靶向BCMA的CAR-T 细胞疗法用于治疗MM。本综述独特地审视了BCMA CAR-T 细胞的整体格局,重点关注识别结构域的设计、临床疗效和患者结局。它批判性地探讨了伴随治疗进展而出现的抗原逃逸和毒性特征等新兴挑战。

此外,本综述聚焦前沿进展,包括双靶点CAR-T 策略、CAR-T 细胞生产的进步,以及利用健康供体细胞的创新性异体CAR-T 方法。通过详细阐述BCMA CAR-T 细胞疗法的突破与持续挑战,本综述提供了关于MM的CAR-T 细胞疗法当前状态和未来可能性的全面视角,及其在治疗血液系统恶性肿瘤及其他疾病中不断扩展的作用。

展开英文摘要原文

Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking immunotherapy, demonstrating significant efficacy in treating B cell malignancies. In the context of multiple myeloma (MM), B cell maturation antigen (BCMA) has been identified as a critical target, driving the development of CAR T cell therapies designed to address this plasma cell cancer.

Various CAR designs, utilizing different BCMA recognition domains, have yielded promising clinical results, leading to the approval of two BCMA-targeting CAR T cell therapies by the US Food and Drug Administration (FDA) for the treatment of MM. This review uniquely examines the BCMA CAR T cell landscape, emphasizing the design of recognition domains, clinical efficacy, and patient outcomes. It critically addresses emerging challenges such as antigen escape and toxicity profiles, which have surfaced alongside therapeutic advances.

Moreover, the review spotlights cutting-edge developments, including dual-targeting CAR T strategies, advancements in CAR T cell manufacturing, and innovative allogeneic CAR T approaches utilizing healthy donor cells. By detailing both the breakthroughs and ongoing challenges in BCMA CAR T cell therapy, this review offers a comprehensive perspective on the current state and future possibilities of CAR T cell therapy for MM and its expanding role in treating hematologic malignancies and beyond.

论文信息

作者
Hu Y、Xie Y、Wang X、Yang L、Geng H、Yi Z、Zhang Y、Ma L
第一作者单位
Department of Anesthesiology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, China.China
通讯作者单位
Department of Anesthesiology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, China. fangchen18938690929@gmail.com.China
文献类型
综述
期刊
Cancer immunology, immunotherapy : CII2025 Feb 1
原文标识
PubMed 39891674 · DOI 10.1007/s00262-024-03913-0