Antibody Directed Enzyme Prodrug Therapy (ADEPT): Trials and tribulations.

Antibody directed enzyme prodrug therapy has the potential to be an effective therapy for most common solid cancers. Clinical studies with CPG2 system have shown the feasibility of this approach. The key limitation has been immunogenicity of the enzyme.

Translating antibody directed enzyme prodrug therapy (ADEPT) and prospects for combination.

The generation of cytotoxic drugs, selectively within tumours, from non-toxic prodrugs by targeted enzymes provides a powerful system for cancer therapy. In the form of Antibody directed enzyme prodrug therapy (ADEPT), this approach has shown feasibility in the clinic. Areas covered: Although numerous enzyme prodrug combinations have been reported over the last two decades, only the CPG2 ADEPT system has progressed to clinical trials.

Trophoblastic reminiscences.

Development of the radioimmunoassay in the 1950s and early '60s largely eliminated early problems with human chorionic gonadotropin and permitted the U.K. to offer a national service for gestational trophoblastic disease (GTD) patients.

Antibody-directed enzyme prodrug therapy (ADEPT) for cancer.

Antibody-directed enzyme prodrug therapy was conceived as a means of restricting the action of cytotoxic drugs to tumor sites. Since antigenic targets were a central component of the approach, colonic cancer, with its virtually universal expression of carcinoembryonic antigen at the cellular level, presented an obvious starting point. The principle of antibody-directed enzyme prodrug therapy is to use an antibody directed at a tumor-associated antigen to vector an enzyme to tumor sites.

Advances in antibody-directed enzyme prodrug therapy.

Antibody-directed enzyme prodrug therapy has demonstrated feasibility as a treatment for cancer. Numerous prodrug/drug systems have been developed for activation by a variety of enzymes and although many have shown potential in preclinical studies, so far only one system has progressed to the clinic. Clinical studies have identified issues that were not readily apparent in xenograft models, however, these have not been addressed in the development and testing of new prodrugs.

Antibody-directed enzyme prodrug therapy (ADEPT) for cancer.

Antibody-directed enzyme prodrug therapy (ADEPT) aims to restrict the cytotoxic action to tumour sites. The obstacles to achieve this were recognised at the outset, but time and experience have given these better definition. The development of fusion proteins has provided the means of making consistent antibody-enzyme constructs on an adequate scale, and glycosylation has provided the means to control the clearance of enzyme from non-tumour sites.