The successful identification of novel tumor antigens is critical to cancer immunotherapy and its potential use in cancer prevention. Colon cancer is the third most common cancer in both men and women and is the second most common cause of cancer death. Rodent models (Apc Min, AOM induced tumors in mice and rats) that mimic human disease provide a unique tool for tumor antigen discovery. There are varieties of approaches towards deciding upon antigens that might be employed to develop a vaccine. In the case where there is a highly over expressed protein that appears to be directly associated with tumor development (e.g., Neu in Neu over-expressing tumors), this appears to be a promising approach both in animal models and clinically. A second approach is to pick antigens which are over expressed in both mouse and human tumors, and which appear to be associated with the tumor process. It is this latter approach that the studies will employ here. The specific animal model the studies will employ here is a modified ApcMin or Min mouse model. Although the standard Min model, on a C57BL6 background, has proven effective in screening potential chemopreventive agents, it has a major limitation for vaccine studies. The adenomas arise rapidly so that an animal will already have multiple adenomas at the time that immunization is initiated. Furthermore, Min adenomas rarely progress to full carcinomas, which may be due to shortened lifespan as almost all Min mice die by ~100 days of age due to tumor burden. To overcome this, the studies will be conducted with an F1 Min mouse (C57BL/6-APCMin/J x AKR). In this case, tumors arise more slowly, which allows immunization of animals with minimal tumor burden. F1 Min animals survive long enough (up to 300 days) that they develop adenocarcinomas in the small intestine and a significant number of lesions of the colon unlike the standard Min mice.
