In certain embodiments, methods and compositions are provided for generating immune responses against tumor antigens such as antigens or epitopes of HER1, HER2/neu, HER3, HER4, or any combination thereof. In particular embodiments, there may be provided methods for constructing and producing recombinant adenovirus-based vector vaccines containing nucleic acid sequences encoding tumor antigens such as antigens or epitopes of HER1, HER2/neu, HER3, HER4, or any combination thereof, that allow for vaccinations in individuals with preexisting immunity to adenovirus.