A dual-enzyme cleavable linker for antibody–drug conjugates

Abstract

A novel enzyme cleavable linker for antibody–drug conjugates is reported. The 3-O-sulfo-β-galactose linker is cleaved sequentially by two lysosomal enzymes – arylsulfatase A and β-galactosidase – to release the payload in targeted cells. An α-HER2 antibody–drug conjugate synthesised using this highly hydrophilic dual-cleavable linker exhibited excellent cytotoxicity and selectivity.