Antibody-Drug Conjugates: The Last Decade.

Antibody-Drug Conjugates: The Last Decade.
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DOI:
10.3390/ph13090245
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发表时间:
2020-09-14
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
Denevault-Sabourin C
Denevault-Sabourin C
中科院分区:
其他
文献类型:
--
作者:
Joubert N;Beck A;Dumontet C;Denevault-Sabourin C

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武装抗体(抗体-药物缀合物或ADC)是一种载体化化疗,其通过明智构建的间隔臂将细胞毒性剂接枝到单克隆抗体上。ADC在10年内取得了相当大的进展。虽然在2009年只有吉妥珠单抗(Mylotarg®)被临床使用,但在2020年,有9种美国食品药品监督管理局(FDA)批准的ADC可用,另有80多种正在进行临床研究。本综述将重点关注FDA批准的晚期ADC,它们的局限性,包括它们的毒性和相关的耐药机制,以及解决这些问题的新策略,并试图扩大它们的治疗窗口。最后,我们将讨论它们与常规化疗或检查点抑制剂的组合,以及它们在肿瘤学之外的应用设计,使ADC成为Paul埃利希梦想的神奇子弹。
An armed antibody (antibody–drug conjugate or ADC) is a vectorized chemotherapy, which results from the grafting of a cytotoxic agent onto a monoclonal antibody via a judiciously constructed spacer arm. ADCs have made considerable progress in 10 years. While in 2009 only gemtuzumab ozogamicin (Mylotarg®) was used clinically, in 2020, 9 Food and Drug Administration (FDA)-approved ADCs are available, and more than 80 others are in active clinical studies. This review will focus on FDA-approved and late-stage ADCs, their limitations including their toxicity and associated resistance mechanisms, as well as new emerging strategies to address these issues and attempt to widen their therapeutic window. Finally, we will discuss their combination with conventional chemotherapy or checkpoint inhibitors, and their design for applications beyond oncology, to make ADCs the magic bullet that Paul Ehrlich dreamed of.
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