A plasmid DNA cancer vaccine encoding the intracellular domain (ICD) of the HER-2/neu proto-oncogene. Upon administration and after cellular uptake by skin or muscle cells, the pNGVL3-hICD vaccine plasmid expresses the HER-2/neu protein, which, after intracellular processing, may elicit both antigen-specific cytotoxic T-lymphocyte (CTL) and humoral immune responses against tumor cells expressing HER-2. The HER-2/neu ICD protein is highly immunogenic and, as a subdominant epitope, may be associated with decreased immune tolerance.