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 both in men and women and is the second most common cause of cancer death. Mouse models that mimic human disease provide a unique tool for tumor antigen discovery. In the past, multiple groups have used a variety of rodent models of colon cancer (Min, AOM Mouse, AOM Rat) to examine colon cancer development, potential agents that can prevent cancer development (e.g. NSAIDs) etc. In a more limited number of cases, they have used these models to examine the role of the immune response and even to make initial examination of immunization against colon cancer.
There are a variety of approaches towards deciding upon antigens which might be employed to develop a vaccine. In the rare cases 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 is to pick antigens which are over expressed in both model and human tumors and which appear to be associated with the tumor process. It is this latter approach that will be employed here.
The specific animal model that will be employed here is a modified Min model. Although the standard Min model, on a C57BL6 background, has proven effective in screening potential chemopreventive agent it has a major limitation for vaccine work. The adenomas arise quite rapidly so that an animal will already have multiple adenomas at the time that immunization is initiated. To overcome this, the Contractor shall employ an F1 Min mouse (C57BlxAKR). In this case tumors come up more slowly which allows for initial immunization of animals with minimal tumor burden. Furthermore, animals survive long enough that they develop adenocarcinomas in the small intestine and a significant number of lesions of the colon unlike the standard Min mice.