MMP-cleavable linker platform for tumour-responsive homo- and heterobivalent antibody–drug conjugates

Abstract

Herein we report the development of a novel linker platform for tumour-responsive antibody–drug conjugates. A series of functionalised homo- and heterobivalent BisFab conjugates have been synthesised, comprising an MMP-cleavable peptide sequence which facilitates selective monomerisation in the tumour microenvironment of the BisFab into two smaller cytotoxic species. The platform was then expanded to produce bispecific BisFab conjugates.