Andrew J. Counsell, Stephen J. Walsh, Nicola Ashman, Mahri Park, Friederike M. Dannheim, Thomas A. King, Thomas Wharton, Jason S. Carroll, David R. Spring
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.