Antibody-Directed Enzyme Prodrug Therapy (Adept) For Cancer

Antibody-directed enzyme prodrug therapy (ADEPT) is a system that aims to restrict the action of a high concentration of a cytotoxic drug to cancer sites. This is achieved by using an antibody (or antibody fragment) to deliver a non-human enzyme to cancer sites.To avoid systemic toxicity, enzyme levels in blood must be very low at the time of prodrug administration. The rapid clearance of enzyme from blood may be achieved by either using a glycosylated fusion molecule or by addition of a second component that inactivates the enzyme before a non-toxic prodrug that is a substrate for the enzyme is given. The low molecular weight drug thus generated diffuses through the tumour mass but has a short half-life so that it does not reach normal cell renewal system.;. Many pre-clinical studies using a variety of enzymes and prodrugs confirmed efficacy of this approach but only one system has progressed to clinical trials. These clinical studies identified new challenges that need to be addressed when developing new ADEPT systems.