更好地了解适应性和先天免疫系统在包括多发性骨髓瘤 (MM) 在内的癌症发生中的作用，促进了新型免疫疗法的开发。 B 细胞成熟抗原 (BCMA)、G 蛋白偶联受体家族 C 组 5 成员 D (GPRC5D) 和 Fc 受体样蛋白 5 (FcRL5，也称为 FcRH5) 是浆细胞表达的细胞表面跨膜蛋白，具有已被确定为 MM 的重要免疫治疗靶点，在经过大量预处理的复发和/或难治性疾病患者中表现出有希望的活性。事实上，自 2020 年以来，针对 BCMA 或 GPRC5D 的抗体药物偶联物、双特异性 T 细胞接合剂和自体嵌合抗原受体 T 细胞已被批准用于治疗复发和/或难治性 MM。然而，对这些疗法的反应并不普遍，并且总是会发生获得性耐药。在这篇综述中，我们讨论了针对 BCMA、GPRC5D 和 FcRL5 的各种免​​疫治疗方法，这些方法目前可用于或正在临床开发中，用于 MM 患者。我们还回顾了对此类疗法产生耐药性的机制，并讨论了克服这些机制并改善患者治疗效果的潜在策略。© 2024。Springer Nature Limited。

A better understanding of the roles of the adaptive and innate immune systems in the oncogenesis of cancers including multiple myeloma (MM) has led to the development of novel immune-based therapies. B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D) and Fc receptor-like protein 5 (FcRL5, also known as FcRH5) are cell-surface transmembrane proteins expressed by plasma cells, and have been identified as prominent immunotherapeutic targets in MM, with promising activity demonstrated in patients with heavily pretreated relapsed and/or refractory disease. Indeed, since 2020, antibody-drug conjugates, bispecific T cell engagers and autologous chimeric antigen receptor T cells targeting BCMA or GPRC5D have been approved for the treatment of relapsed and/or refractory MM. However, responses to these therapies are not universal, and acquired resistance invariably occurs. In this Review, we discuss the various immunotherapeutic approaches targeting BCMA, GPRC5D and FcRL5 that are currently either available or in clinical development for patients with MM. We also review the mechanisms underlying resistance to such therapies, and discuss potential strategies to overcome these mechanisms and improve patient outcomes.© 2024. Springer Nature Limited.