肿瘤细胞治疗研究
英文原题：Just scratching the surface: novel treatment approaches for multiple myeloma targeting cell membrane proteins.
对适应性免疫系统和固有免疫系统在包括多发性骨髓瘤（MM）在内的癌症发生中所起作用有了更深入的了解，这促进了新型免疫疗法的开发。
对适应性免疫系统和固有免疫系统在包括多发性骨髓瘤（MM）在内的癌症发生中所起作用有了更深入的了解，从而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第5组成员D（GPRC5D）和Fc受体样蛋白5（FcRL5，也称为FcRH5）是由浆细胞表达的细胞表面跨膜蛋白，已被确定为MM中重要的免疫治疗靶点，在既往接受过大量治疗的复发和/或难治性疾病患者中显示出有前景的活性。事实上，自2020年以来，靶向BCMA或GPRC5D的抗体-药物偶联物、双特异性T细胞衔接器和自体CAR-T 细胞已获批用于复发和/或难治性MM的治疗。然而，对这些疗法的应答并非普遍存在，获得性耐药不可避免地会发生。在本综述中，我们讨论了目前可用于MM患者或处于临床开发阶段的靶向BCMA、GPRC5D和FcRL5的各种免疫治疗策略。我们还综述了此类疗法耐药的机制，并讨论了克服这些机制和改善患者预后的潜在策略。
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.
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