<U>Gene Discovery</U>- Immunotherapy has been most successful when targeted to differentiation antigens expressed on hematopoietic tumors in large part because the target antigens are not expressed on essential cells or organs. Other cancers in which this approach could be successful are prostate, breast and ovary. To identify target antigens in prostate and breast cancers we have developed a computer based method to search the EST data base for ESTs that are expressed in prostate or breast cancer and not in other essential organs or cells. We have validated this approach experimentally and used it to identify several genes/proteins expressed in prostate cancer or breast and not in essential normal organs. We are focusing our efforts on four of these: NGEP, CAPC and POTE. NGEP is a membrane protein that appears to have a role in the adhesion of prostate cancer cells to each other. CAPC is associated with cytokeratin and is highly expressed in many cancers during mitosis. POTE is assiciated with the inner aspect of the plasma membrane where it interests with the cytoskeleton. Mesothelin is a protein found on the surface of mesotheliomas, ovarian cancers and pancreatic cancers. It is a target for the immunotherapy of mesothelioma, ovarian cancer and pancreatic cancer.