Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?
Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?
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DOI：
10.3390/ph16040590
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发表时间：
2023-04-14
期刊：
影响因子：
--
通讯作者：
Orlowski RZ
中科院分区：
文献类型：
--
作者：
Ray U;Orlowski RZ
多发性骨髓瘤是一种分泌免疫球蛋白的浆细胞恶性肿瘤，目前在初诊以及复发和/或难治性情况下，经常使用针对谱系特异性标志物的单克隆抗体进行治疗，这些抗体可单独使用，也可用于合理设计的联合方案中。其中包括抗CD38抗体达雷妥尤单抗和伊沙妥昔单抗，以及抗信号淋巴细胞激活分子家族成员7抗体埃罗妥珠单抗，它们均以非偶联形式使用。抗体的单链可变片段也是靶向B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T细胞产品伊基奥仑赛和西达基奥仑赛中CAR的关键组成部分，这些产品已被批准用于晚期患者。最近，双特异性抗BCMA和T细胞衔接抗体特立妥单抗也已上市，同样用于复发/难治性疾病患者。抗体可转化为发挥抗肿瘤功效的另一种形式是抗体 - 药物偶联物（ADCs），同样靶向BCMA的贝兰他单抗莫福汀是首个在骨髓瘤治疗中立足的此类药物。最近一项III期研究的阴性结果促使启动了撤回其上市许可的程序。然而，贝兰他单抗仍然是一种有一定前景的药物，许多其他靶向BCMA或其他浆细胞表面标志物的ADCs正在研发中并显示出潜力。本文将概述一些当前数据，这些数据支持ADCs在未来仍将是我们治疗骨髓瘤的化疗方案的一部分这一可能性，并强调未来的发展方向。
Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved in the advanced setting. Most recently, the bispecific anti-BCMA and T-cell-engaging antibody teclistamab has become available, again for patients with relapsed/refractory disease. Another format into which antibodies can be converted to exert anti-tumor efficacy is as antibody–drug conjugates (ADCs), and belantamab mafodotin, which also targets BCMA, represented the first such agent that gained a foothold in myeloma. Negative results from a recent Phase III study have prompted the initiation of a process for withdrawal of its marketing authorization. However, belantamab remains a drug with some promise, and many other ADCs targeting either BCMA or other plasma cell surface markers are in development and showing potential. This contribution will provide an overview of some of the current data supporting the possibility that ADCs will remain a part of our chemotherapeutic armamentarium against myeloma moving forward, and also highlight areas for future development.
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影响因子：
3.7
作者：
Aoyama M;Tada M;Yokoo H;Demizu Y;Ishii-Watabe A
通讯作者：
Ishii-Watabe A
影响因子：
5.7
作者：
通讯作者：
--
影响因子：
--
作者：
Abrahams, Cristina L;Li, Xiaofan;Molina, Arturo
通讯作者：
Molina, Arturo
DOI：
10.1158/1078-0432.ccr-22-0618
发表时间：
2022-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
通讯作者：
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影响因子：
10.3
作者：
DREWINKO, B;ALEXANIAN, R
通讯作者：
ALEXANIAN, R