A dual-enzyme cleavable linker for antibody–drug conjugates
Jonathan D. Bargh, Stephen J. Walsh, Nicola Ashman, Albert Isidro‐Llobet, Jason S. Carroll, David R. Spring
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.
Topics & Concepts
LinkerConjugateEnzymeChemistryAntibody-drug conjugateDrugBiochemistryAntibodyCombinatorial chemistryBiologyPharmacologyMonoclonal antibodyImmunologyComputer scienceMathematicsMathematical analysisOperating systemMonoclonal and Polyclonal Antibodies ResearchHER2/EGFR in Cancer ResearchGlycosylation and Glycoproteins Research