Development of a novel enzyme/prodrug combination for gene therapy of cancer: horseradish peroxidase/indole-3-acetic acid

This paper demonstrates the potential for utilizing the plant enzyme, horse radish peroxidase (HRP), in a gene-directed enzyme prodrug therapy context. Human T24 bladder carcinoma cells transfected with a mammalian expression vector containing the HRP cDNA were selectively sensitized to the nontoxic plant hormone, indole-3-acetic acid (IAA). The HRP/IAA-induced cell kill wa s effective in normoxic and anoxic conditions. The activated drug is a long -lived species able to cross cell membranes, and cell contact appears not t o be required for a bystander effect to take place. These preliminary resul ts suggest that the delivery of the HRP gene to human tumors followed by IA A treatment may provide a novel cancer gene-directed enzyme prodrug therapy approach, with potential to target hypoxic cells.