Antibody-directed enzyme prodrug therapy (ADEPT): a review

Antibody-directed enzyme prodrug therapy (ADEPT) is a therapeutic strategy which aims to improve the selectivity of anticancer drugs. ADEPT is a two-step antibody targeting system that has benefits over a one-step chemo-, toxin- or radioimmunoconjugate. The basic principles of ADEPT are discussed alongside the requirements of the components: antibodies, enzymes and prodrugs. The design and syntheses of prodrugs are detailed particularly prodrug/drug systems of potential clinical use, the rationale behind their design and the in vitro and in vivo results obtained. The main features of ADEPT, such as targeting of cancer cells by the antibody-enzyme conjugates, enzymic activation of the prodrugs, selection of the prodrug/drug and enzyme/prodrug systems are reviewed.