The First Generation of b-Galactosidase-Responsive Prodrugs Designed for the Selective Treatment of Solid Tumors in Prodrug Monotherapy

Thibaut Legigan, Jonathan Clarhaut, Isabelle Tranoy-Opalinski, Arnaud Monvoisin,
Brigitte Renoux, Mika l Thomas, Alain Le Pape, St phanie Lerondel, and S bastien Papot

http://onlinelibrary.wiley.com/doi/10.1002/anie.201204935/full

One strategy for treating cancer is antibody-directed enzyme prodrug therapy (ADEPT), in which a prodrug (eg. a galactosidase prodrug) can be used in combination with an antibody-beta-galactosidase conjugate that can bind an antigen on the tumor surface (that is often overexpressed), and release active drug at the site of the tumor. These researchers instead synthesized a galactoside prodrug composed of a targeting ligand, galactoside trigger, and drug that can interact with the tumor's endogenous beta-galactosidases. The researchers were able to show targeting of these drugs and activation in tumor cells, and confirm with studies done in mice.