A dual-enzyme cleavable linker for antibody-drug conjugates

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