Research Project
6889875
DESCRIPTION (provided by applicant): Prostate cancer is the second most common type of cancer found in American men. It is estimated that in 2003 there will be approximately 220,900 new cases of prostate cancer diagnosed with almost 30,000 deaths. The main treatment modalities are surgery, radiation therapy, hormone ablation therapy and chemotherapy. Although there are known risk factors for prostate cancer, there is currently no way to prevent this cancer because its cause remains unknown. One new approach is to mobilize the patient's immune system against his own prostate cancer. This concept of therapeutic vaccination would complement the current arsenal of treatments and provide long-term, systemic protection against recurrence. Another new approach that has been successful in other cancers is radio-immunotherapy, which employs monoclonal antibodies against tumor antigens that are conjugated to a radioactive payload. Discovery of the targets of vaccines and monoclonal antibodies, called tumor antigens, is imperative in order to design immunotherapies that do not destroy normal tissues. Tumor antigens have been described in some human cancers such as melanoma, kidney cancer and breast cancer. The most successful methods of identifying tumor antigens have been to use molecular screening methods of differential gene expression or to employ tumor-reactive cytotoxic T lymphocytes to select antigen-expressing clones from a tumor cDNA library. For prostate cancer, this has been extremely difficult because tumor-reactive T cells are difficult to isolate and grow in vitro, unlike melanoma reactive TIL, which have been technically easier to cultivate. Moreover, it has been difficult to obtain large quantities of tumor because the amount of surgical material obtained is generally minute. We and our collaborators and we have overcome multiple technical obstacles that have hampered identification of prostate tumor antigens. Preliminary data are presented that demonstrate the identification of 14 prostate peptides, over expressed in tumor cells and not normal prostate epithelial cells isolated from a single patient. These were eluted from MHC molecules and characterized by mass spectroscopy. In the present study, these differentially expressed antigens will be validated for broad applicability to vaccine and monoclonal antibody therapy for prostate cancer.
