Antibody‐directed enzyme prodrug therapy: A review

Many of the limitations of conventional cytotoxic chemotherapy and of attempts to achieve selectivity using antibody vectors can be overcome by a 2 or 3 stage prodrug system. An antibody vectors to tumour sites an enzyme that is not normally present in human extracellular fluids. The tumour located enzyme activates a subsequently administered prodrug. As with other antibody based systems the pharmacokinetics and biodistribution of the antibody‐enzyme conjugate are critical elements. In contrast to antibody drug conjugates and radiolabelled antibodies, an enzyme can be inactivated in non‐tumour tissues, or subjected to rapid clearance, without toxic effects, which allows high tumour to normal tissue ratios to be achieved. Enzymes conjugated to antibodies increase the problem of immunogenicity and require either the use of immunosuppressive agents, or the development of non‐immunogenic catalysts. A small scale pilot clinical trial has shown the general feasibility of the approach.