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Focus on monoclonal antibodies targeting B‐cell maturation antigen (BCMA) in multiple myeloma: update 2021

嵌合抗原受体 医学 单克隆抗体 多发性骨髓瘤 抗原 免疫疗法 抗体 免疫学 临床试验 癌症研究 内科学 免疫系统
作者
Ivo Demel,Julio Rodriguez Bagó,Roman Hájek,Tomáš Jelı́nek
出处
期刊:British Journal of Haematology [Wiley]
卷期号:193 (4): 705-722 被引量:20
标识
DOI:10.1111/bjh.17235
摘要

Abstract Remarkable advances have been achieved in the treatment of multiple myeloma (MM) in the last decade, which saw targeted immunotherapy, represented by anti‐CD38 monoclonal antibodies, successfully incorporated across indications. However, myeloma is still considered curable in only a small subset of patients, and the majority of them eventually relapse. B‐cell maturation antigen (BCMA) is expressed exclusively in mature B lymphocytes and plasma cells, and represents an ideal new target for immunotherapy, presented by bispecific antibody (bsAb) constructs, antibody‐drug conjugates (ADCs) and chimeric antigen receptor T (CAR‐T) cells. Each of them has proved its efficacy with the potential for deep and long‐lasting responses as a single agent therapy in heavily pretreated patients. As a result, belantamab mafodotin was approved by the United States Food and Drug Administration for the treatment of relapsed/refractory MM, as the first anti‐BCMA agent. In the present review, we focus on monoclonal antibodies targeting BCMA – bsAbs and ADCs. The data from preclinical studies as well as first‐in‐human clinical trials will be reviewed, together with the coverage of their constructs and mechanisms of action. The present results have laid the groundwork for the ongoing or upcoming clinical trials with combinatory regimens, which have always been a cornerstone in the treatment of MM.
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