奥佐美星
卡奇霉素
医学
细胞毒性
单克隆抗体
免疫结合物
抗体
抗体-药物偶联物
药品
药物开发
结合
药理学
癌症研究
免疫学
CD33
化学
生物
体外
生物化学
干细胞
川地34
数学分析
遗传学
数学
作者
Elias Jabbour,Paul Stolzmann,Hagop M. Kantarjian
标识
DOI:10.1038/s41571-021-00484-2
摘要
Advances in our understanding of cancer biology have enabled drug development to progress towards better targeted therapies that are both more effective and safer owing to their lack of off-target toxicities. In this regard, antibody-drug conjugates (ADCs), which have the potential to combine the selectivity of therapeutic antibodies with the cytotoxicity of highly toxic small molecules, are a rapidly developing drug class. The complex and unique structure of an ADC, composed of a monoclonal antibody conjugated to a potent cytotoxic payload via a chemical linker, is designed to selectively target a specific tumour antigen. The success of an ADC is highly dependent on the specific properties of its components, all of which have implications for the stability, cytotoxicity, pharmacokinetics and antitumour activity of the ADC. The development of therapeutic ADCs, including gemtuzumab ozogamicin and inotuzumab ozogamicin, provided great knowledge of the refinements needed for the optimization of such agents. In this Review, we describe the key components of ADC structure and function and focus on the clinical development and subsequent utilization of two leukaemia-directed ADCs - gemtuzumab ozogamicin and inotuzumab ozogamicin - as well as on the mechanisms of resistance and predictors of response to these two agents.
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