The Design and Synthesis of Prodrugs for Antibody-Directed Enzyme Prodrug Therapy (ADEPT)

Abstract

Antibody-directed enzyme prodrug therapy (ADEPT) is a strategy for treating cancer that combines antibody specificity with enzymatic catalysis to deliver drugs selectively to tumor sites. In this approach a conjugate consisting of an enzyme chemically linked to a tumor-selective antibody (mAb) is administered to the host and allowed to localize at the tumor site. After a suitable interval to allow clearance of the conjugate from the blood, a non-toxic prodrug is administered which releases a therapeutic drug on contact with the enzyme. This two-step approach has the potential to overcome many of the limitations of current chemotherapeutic strategies, allow the generation of high intratumoral concentrations of drug, and minimize damage to normal tissues.