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多发性骨髓瘤中的 CAR-T 细胞治疗:B 细胞成熟抗原(BCMA)及更多

英文原题:CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond.

PubMed 2023/11/16(内容时间) Vaccines (Basel) Q2 · IF 3.5(JCR 2025)

研究概要

多发性骨髓瘤 (MM) 的治疗干预领域已取得重大进展,导致其临床管理发生变革性转变。

中文摘要

多发性骨髓瘤(MM)治疗取得显著进展,临床管理方式因此发生变革。手术、放疗和化疗等传统治疗改善了临床结局,但复发/难治性MM(RRMM)患者仍面临难以实现全面治愈这一核心挑战。过继细胞疗法,尤其是CAR-T 细胞疗法,已在难治或耐药的B细胞恶性肿瘤患者中显示疗效,目前也正在MM患者中开展试验。在此背景下,B细胞成熟抗原(BCMA)成为MM CAR-T细胞治疗有前景的靶抗原。其他潜在靶点包括SLAMF7、CD38、CD19、信号淋巴细胞活化分子CS1、NKG2D及CD138。多项临床研究已显示这些CAR-T疗法具有临床疗效,但长期随访发现存在一定程度的抗原逃逸。CAR-T广泛应用仍受多种障碍限制,包括抗原逃逸、实体瘤中瘤内浸润不均、细胞因子释放综合征、神经毒性、实施流程复杂及经济负担。本文概述CAR-T治疗MM的情况及BCMA作为靶抗原的应用,并介绍其他潜在靶点分子。

展开英文摘要原文

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.

论文信息

作者
Mishra AK、Gupta A、Dagar G、Das D、Chakraborty A、Haque S、Prasad CP、Singh A
第一作者单位
Molecular, Cellular and Developmental Biology Department, University of California Santa Barbara, Santa Barbara, CA 93106, USA.United States
通讯作者单位
Department of Medical Oncology (Lab), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.India
文献类型
综述
期刊
Vaccines2023 Nov 16
原文标识
PubMed 38006053 · DOI 10.3390/vaccines11111721