Gene-based therapy for localized prostate cancer?

Posted on October 25, 2010 by Sitemaster

An Australian company called Broadvector is initiating a Phase I clinical trial of a new two-stage, gene-based therapy for the treatment of prostate cancer.

The company’s technology is based on direct intraprostatic injection of a gene vector carrying a specific gene that codes for a therapeutic enzyme. After a brief incubation period, a small molecule (a “pro-drug”) is then administered. The pro-drug is converted (presumably by the therapeutic enzyme) to an active drug in the target tissue. The company refers to this form of treatment as “gene-directed enzyme pro-drug therapy” or GDEPT.

In theory, this technology would potentially be most applicable to men with localized prostate cancer. However, the initial Phase I trial will take place at St Vincent’s Hospital in Sydney on about 20 men who have “no other treatment options.” No patients have been treated with this form of therapy to date, but the trial is expected to begin in the near future.

A television news report about this technology — based on the work of a virologist at the Australian CSIRO — is available on the company’s web site. Apparently the viral carrier technology used to introduce the initial gene into the prostate is based on a sheep virus — ovine atadenovirus (which only seems appropriate for an Australian biotech company).

According to the company’s prospectus, the ovine atatenovirus is used to introduce “a proprietary therapeutic gene” directly into the prostate. Shortly thereafter, the pro-drug (a well-known drug called fludarabine, widely used in the treatment of leukemias) is also injected into the prostate over a period of 5 days. Although fludarabine itself has no effect on prostate cancer, the company claims that fludarabine is converted (by an enzyme known as purine nucleoside phosphorylase or PNP) into an active drug called 2-fluoroadenine, which is capable of killing prostate cancer cells (whether they are indolent or rapidly dividing).

Whether this type of therapy will actually work effectively and safely in prostate cancer patients is obviously not known at the present time. But even if the initial Phase I trial is successful, it could still take years to bring a treatment like this to market. The company’s statement that this technology will initially be tested on men who “have no other treatment options” is not entirely clear. (This could mean they are men who have metastatic, castration-resistant prostate cancer that has failed other forms of treatment, and that the objective of this Phase I trial is only to test whether the technology is active in men with prostate cancer who still have an intact prostate.)