(Gong, et al., 1999; Kondo, et al., 2000; Voeks, et al., 2002). A gene-directed enzyme pro-drug therapy (GDEPT) is yet another method in which prostate cancer cells are specifically targeted for destruction. This process involves using a recombinant adenovirus to deliver a PNP gene into the cancer cell which causes the cell to convert purine pro-drugs into toxic metabolites. (Voeks, et al., 2002). Thus by administering a prodrug like fludarabine phosphate to patients with prostate cancer only the cells infected by the OAdV220 virus would break down the fludarabine phosphate into a compound that is toxic to the cell. (Voeks, et al., 2002). .
In humans, high doses of fludarabine phosphate can cause myelosuppression, the suppression of bone marrow activity, resulting in reduction in the number of platelets, red cells and white cells found in the circulation. With mice that carried human prostate cancer cells, the effective dose was 75 mg/m2/day. In humans the dosage usually used is 25 mg/m2/day for a series of treatments, each for 5 days, extended for up to 30 courses with cumulative toxicity. It is expected that future GDEPT studies will be performed with lower doses of pro-drug to understand how low a fludarabine phosphate dose can be used to achieve maximum efficiency (Voeks, et al., 2002).
Another experimental form of treatment for prostate cancer involves the construction of a novel chain fusion receptor named Pz-1 specific for the prostate-specific membrane antigen (PSMA). PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and its expression is increased in the later stages of advanced prostate cancer, which include metastatic cells as well as hormone-deprived cells (Gong, et al., 1999). Gene transfer efficiency was monitored by fluorescence-activated cell sorter and gene take up by the T cells varied between 20% and 50% in a cultured medium. Results show that upon contact, these T cells readily lyse prostate cancer cells.
