A replication-defective, recombinant adenoviral serotype 5 (Ad5) encoding human guanylyl cyclase C (hGCC) and the synthetic Pan DR epitope (PADRE), with potential antineoplastic and immunomodulating activities. Upon intramuscular administration, the Ad5-hGCC-PADRE vaccine expresses hGCC, which may induce both humoral and cellular immune responses against tumor cells expressing the hGCC antigen. This results in the immune-mediated inhibition of tumor cell proliferation, and leads to tumor death. The hGCC protein is normally restricted to intestinal epithelial cells but is overexpressed by metastatic colorectal tumors. PADRE is a helper T-lymphocyte epitope that is able to augment the magnitude and duration of the cytotoxic T-lymphocyte (CTL) response.