We are trying to develop vaccines as a treatment for prostate cancer. It is well known that patients with prostate cancer who have been treated with surgery or radiation therapy, but then have a rising PSA blood test, are at high risk for the cancer progressing and eventually being seen on bone scans and/or CT scans. This stage of prostate cancer, in which patients have been treated for prostate cancer but have a rising blood PSA without other evidence of metastatic disease, is called "stage D0." We believe that this stage of disease, when the cancer is small enough that it is only detectable by the PSA blood test, is a good time to test vaccines. Our hope in using vaccines is that we can enable the immune system to recognize and "reject" prostate cancer cells. We have been studying vaccines targeting a protein that is only made by prostate cells called prostatic acid phosphatase (PAP). We have been studying vaccines in rats, because rats also make a prostate-specific PAP protein. We have shown that rats can be immunized with DNA encoding PAP, and they develop immune responses that we predict would be therapeutic to attack prostate cancer cells.

In the trial proposed here, we want to test this same vaccine in patients with stage D0 prostate cancer. We have previously received funding to have the vaccine manufactured, and we have tested it in rats. It was shown to be safe and effective in eliciting immune responses to PAP. In this trial, we will give a group of patients a low dose of the vaccine, along with a protein called "GM-CSF" that is used to help stimulate an immune response to the vaccine. Because this is the first time this vaccine will be administered to humans, our main goal is to make sure this vaccine is safe. If it appears safe in a small number of patients, we will give another group a larger dose of the vaccine. Our plan is to test three different doses. At the highest dose that appears safe, we will enroll more patients to further test safety and to determine how effective the vaccine is in eliciting a specific type of immune response. We believe that for the vaccine to be effective, it should elicit a certain type of immune system cell (CD8 T cell) that secretes a protein (interferon-gamma) when exposed to the PAP protein. In addition, we will test to see whether patients that receive the vaccine have a change in the serum PSA after completing the immunization series.

Other groups have been testing vaccine strategies targeting this same PAP protein, but using more complicated means of delivering the vaccine. One of these strategies is in advanced clinical testing, with results so far suggesting that patients benefit and live longer after receiving the vaccine. If our trial is successful in eliciting the kind of immune response we think will be most effective, and if people immunized have responses in the PSA blood test, we think this will be a significant accomplishment. These findings would suggest that our vaccine strategy, much simpler than other approaches, could be further developed as a therapy for prostate cancer. In addition, the careful immunology studies that we propose with this study will help us to design more potent vaccines targeting this protein in the future.