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G 蛋白偶联受体 C 类 5 组成员 D 靶向免疫治疗在多发性骨髓瘤中的新兴作用:进展、耐药与联合策略

英文原题:Emerging role of G protein-coupled receptor class C group 5 member D-directed immunotherapy in multiple myeloma: Advances, resistance and combination strategies.

PubMed 2025/08/29(内容时间) Br J Haematol Q2 · IF 3.6(JCR 2025)

研究概要

多发性骨髓瘤(MM)是一种浆细胞克隆性恶性肿瘤,以频繁复发和治疗耐药为特征。

中文摘要

多发性骨髓瘤(MM)是一种浆细胞克隆性恶性肿瘤,常出现复发和治疗耐药。G蛋白偶联受体C类第5组D成员(GPRC5D)在MM细胞中高表达且具有选择性,在正常组织中的表达极少,因此已成为有前景的免疫治疗靶点。本综述概述GPRC5D的结构特征和表达谱,并强调其与疾病生物学及预后的相关性。我们重点介绍GPRC5D靶向疗法的近期进展,包括抗体药物偶联物(ADC)、双特异性及三特异性抗体,以及CAR-T(CAR-T)/自然杀伤(NK)细胞疗法;这些方法在复发或难治性MM中均显示出令人鼓舞的疗效。文章还讨论抗原逃逸及优化联合治疗策略等关键挑战。随着靶向GPRC5D药物进入临床开发阶段,仍需大规模前瞻性试验明确其治疗定位并改善患者结局。继B细胞成熟抗原之后,GPRC5D有望成为MM免疫治疗的新一代重要靶点。

展开英文摘要原文

Multiple myeloma (MM) is a clonal malignancy of plasma cells characterized by frequent relapse and therapeutic resistance. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a promising immunotherapeutic target due to its high and selective expression in MM cells and minimal presence in normal tissues. This review outlines the structural features and expression profile of GPRC5D, emphasizing its relevance to disease biology and prognosis. We highlight recent advances in GPRC5D-targeted therapies, including antibody-drug conjugates (ADCs), bispecific and trispecific antibodies and chimeric antigen receptor T (CAR T)/natural killer (NK)-cell therapies, all demonstrating encouraging efficacy in relapsed/refractory MM. Key challenges, such as antigen escape and the need for optimized combination strategies, are also discussed. As GPRC5D-targeted agents advance through clinical development, large-scale prospective trials will be essential to define their therapeutic positioning and improve patient outcomes. GPRC5D is poised to become a leading next-generation target in MM immunotherapy following B-cell maturation antigen.

论文信息

作者
Wang X、Cui Y、Wang Y、Fang B
单位
Department of Hematology, Henan Institute of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.China
文献类型
综述
期刊
British journal of haematology2025 Nov
原文标识
PubMed 40879107 · DOI 10.1111/bjh.70116