Triggered drug release from an antibody-drug conjugate using fast "click-to-release" chemistry in mice

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 (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

99 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1697-1706
Number of pages10
JournalBioconjugate Chemistry
Volume27
Issue number7
DOIs
Publication statusPublished - 20 Jul 2016

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