Antibody-Directed Enzyme Prodrug Therapy

Synonyms

ADEPT

Definition

Antibody-directed enzyme-prodrug therapy (ADEPT) is a two-step concept for the immunologically targeted application of chemotherapeutic agents to tumor tissue. In it, first a tumor-specific antibody coupled to a prodrug-specific enzyme is applied systemically via a parenteral route. Once this antibody-enzyme-construct has bound to its cognate antigen in tumor tissue and the unbound remainder has cleared from the bloodstream, the prodrug is administered systemically. Ideally, it is converted into active cytotoxic drug exclusively in tumor tissue by the tumor-bound enzyme component of the targeting construct.

Characteristics

In theory, this concept provides obvious advantages: The cytotoxic drug will only be liberated in tumor tissue and thus the therapeutic index will theoretically be increased by the factor of toxicity of cytotoxic drug compared to prodrug. This means less side effects with the same efficacy or increased efficacy with the same toxicity – the...