Data presented here demonstrate that (1) patients with colorectal cancer can develop significant immune responses to nonmutated proteins that are important in driving the biology of the disease, (2) multi-epitope vaccines designed to elicit tumor specific CD4+ T-cells have potent anti-tumor activity, and (3) vaccines targeting colon cancer associated antigens can have prophylactic efficacy in spontaneous intestinal tumor models. Here, CD4 is linked to colorectal cancer.