Triggered Drug Release from an Antibody–Drug Conjugate Using Fast “Click-to-Release” Chemistry in Mice

详细信息    查看全文

• 作者：Raffaella Rossin ; Sander M. J. van Duijnhoven ; Wolter ten Hoeve ; Henk M. Janssen ; Laurens H. J. Kleijn ; Freek J. M. Hoeben ; Ron M. Versteegen ; Marc S. Robillard
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：July 20, 2016
• 年：2016
• 卷：27
• 期：7
• 页码：1697-1706
• 全文大小：426K
• 年卷期：0
• ISSN：1520-4812

文摘

The use of a bioorthogonal reaction for the selective cleavage of tumor-bound antibody–drug conjugates (ADCs) would represent a powerful new tool for ADC therapy, as it would not rely on the currently used intracellular biological activation mechanisms, thereby expanding the scope to noninternalizing cancer targets. Here we report that the recently developed inverse-electron-demand Diels–Alder pyridazine elimination reaction can provoke rapid and self-immolative release of doxorubicin from an ADC in vitro and in tumor-bearing mice.