Antibody-directed enzyme prodrug therapy.

A 2- or 3-stage system can overcome some of the limitations of antibody-based attempts to restrict the action of cytotoxic agents to tumour sites. These systems use the antibody to direct an enzyme, which is unique to extracellular locations in humans, to tumour sites. The tumour-located enzyme is used to activate a subsequently administered prodrug. As with any antibody-based system, the main limitation lies in the distribution of the antibody or antibody conjugate. However, in contrast to drugs or radioisotopes, an enzyme can be inactivated in nontumour tissues or subjected to rapid clearance without toxic effects. The conjugation of an enzyme to an antibody increases its immunogenicity and may require the administration of immunosuppressive agents or the development of nonimmunogenic fusion proteins. A small scale pilot clinical trial has shown the general feasibility of this approach.