The Phase I study of genes overexpressed in bladder tumors compared to normal tissue has yielded several candidates, of which the most promising is the novel gene product, C35. This gene product is overexpressed in 30 percent of primary bladder tumors as well as 70 percent of primary human breast tumors. Human CD8+ cytotoxic T lymphocytes can be induced that lyse both bladder and breast tumor cells that overexpress C35, but that do not lyse normal C35 negative cells. This indicates that immune tolerance to overexpressed C35 will probably not be an obstacle to vaccination for cancer therapy. A C35-specific monoclonal antibody has been generated and used to determine that C35 is a surface membrane protein that appears to transduce a negative growth signal to the tumor following crosslinking by purified monoclonal antibody. Pre-clinical evaluation of therapeutic applications of C35 vaccines and specific antibody are facilitated by the identification of a murine homologue of C35 that is also overexpressed in some murine tumors. The human C35 specific 2C3 monoclonal antibody is also crossreactive with murine C35 and can, therefore, be tested for clinical benefit alone or in conjunction with vaccination or chemotherapy in this animal model.
This research is directed at developing diagnostics and vaccines specific for bladder and breast cancer.
