I. Niculescu-Duvaz and C. J. Springer* Pages 687 - 706 ( 20 )
<P>Antibody-Directed Enzyme Prodrug Therapy (ADEPT) is a new conceptual approach designed to improve the selectivity of anti-cancer drugs. ADEPT separates the cytotoxic from the targeting function of immunoconjugates in a two phase system that has benefits over one phase chemo-, toxin- or radio-immunoconjugates. <P> This review, while discussing the basic prinicples of ADEPT and the main requirements for all the components (enzymes, prodrugs and antibodies) of the systems, also summarizes the latest results obtained with this technolo gy. The main components of ADEPT are described. These include the targeting of cancer cells by the antibody-enzyme conjugates, the enzymatic activation of the prodrugs, the selection of the prodrug/drug (and/or enzyme/prodrug) systems. A special emphasis has been placed on the prodrug/drug systems, the rationale behind their design and the in vitro and in vivo results obtained with the different types of the prodrugs. <P> The analysis of the advantages and disadvantages of the ADEPT system has led to the potential for clinical use of this sytem, which enables higher drug concentrations at the tumor compared to classical chemotherapy.</P>