Immunity to the HER-2/neu oncogenic protein.

The study of oncogenic viruses led to the discovery that transforming retroviruses contain oncogenes homologous with and/or derived from cellular proto-oncogenes. In humans malignant transformation is often the result of the activation of proto-oncogenes. Normal proto-oncogenes can be activated to transforming proto-oncogenes by a variety of mechanisms including point mutation, translocation and amplification. Development of successful strategies for the immunotherapy of human cancers is an area of intense investigation. Part of the problem in developing cancer-specific immunotherapy has been the lack of well-defined tumour antigens. Our laboratory has focused on the question of whether oncogenic proteins expressed by transforming proto-oncogenes can serve as targets for immune attack. Some patients with HER-2/Neu-positive breast cancer have an existent immune response to the HER-2/neu protein with no clinical signs of autoimmunity, supporting the idea that overexpressed oncogenic proteins can be targeted in therapy without fear of destructive autoimmunity. The identification of candidate cytotoxic T lymphocyte epitopes might allow the generation of tumour-specific cytotoxic T lymphocytes for use in therapy and identify potential epitopes for peptide vaccines.