Given its nearly ubiquitous expression on plasma cells and limited expression on essential normal tissue, the G protein-coupled receptor class C group 5 member D (GPRC5D) presents a promising opportunity for utilization as an immunotherapy target in multiple myeloma (MM). The therapeutic strategies targeting GPRC5D, such as bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T cells, and antibody–drug conjugates (ADCs), have been prominently emphasized in relapsed/refractory MM (R/R MM) in recent years. Further clinical trials are necessary to confirm the long-term efficacy of GPRC5D-targeting immunotherapies alone, explore their potentials co-targeting with other specific antigens, or investigate their combinations with existing treatments to overcome MM resistance. This review provides an overview of current research progress in GPRC5D, encompassing its biological characteristics and translational journey from laboratory to clinical application.

中文翻译：

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靶向 GPRC5D 进行多发性骨髓瘤治疗


鉴于 G 蛋白偶联受体 C 类 5 成员 D (GPRC5D) 在浆细胞上几乎普遍表达，而在基本正常组织中表达有限，因此它为多发性骨髓瘤 (MM) 的免疫治疗靶点提供了一个有希望的机会。近年来，针对 GPRC5D 的治疗策略，如双特异性抗体 (BsAbs)、嵌合抗原受体 (CAR) T 细胞和抗体药物偶联物 (ADC)，在复发/难治性 MM (R/R MM) 中受到重视。需要进一步的临床试验来确认单独的 GPRC5D 靶向免疫疗法的长期疗效，探索它们与其他特定抗原共同靶向的潜力，或研究它们与现有疗法的组合以克服 MM 耐药性。本综述概述了 GPRC5D 目前的研究进展，包括其生物学特性以及从实验室到临床应用的转化历程。