Triggered Drug Release from an Antibody–Drug Conjugate Using Fast “Click-to-Release” Chemistry in Mice
Bioconjugate Chemistry2016Vol. 27(7), pp. 1697–1706
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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
Abstract
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.
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