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Immunity to the HER-2/neu oncogenic protein
M L Disis1, H Bernhard, J R Gralow
1Department of Medicine, University of Washington, Seattle 98195, USA.
Abstract:
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.
Insights
Oncogenic proteins from proto-oncogenes can be targeted for cancer immunotherapy. Research suggests targeting HER-2/neu in breast cancer is safe and effective, paving the way for new cancer vaccines.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Malignant transformation in humans often results from proto-oncogene activation.
- Identifying tumor antigens is crucial for developing effective cancer immunotherapies.
- Oncogenic proteins derived from proto-oncogenes are potential targets for immune attack.
Purpose of the Study:
- To investigate if oncogenic proteins expressed by transforming proto-oncogenes can serve as targets for immune attack.
- To explore the potential of targeting HER-2/neu in breast cancer immunotherapy.
- To identify candidate cytotoxic T lymphocyte epitopes for therapeutic applications.
Main Methods:
- Analysis of oncogenic proteins and their homologous cellular proto-oncogenes.
- Investigation of immune responses in HER-2/Neu-positive breast cancer patients.
- Identification of potential cytotoxic T lymphocyte epitopes.
Main Results:
- Some patients with HER-2/Neu-positive breast cancer exhibit an immune response to HER-2/neu without autoimmunity.
- This suggests overexpressed oncogenic proteins can be therapeutic targets.
- Candidate cytotoxic T lymphocyte epitopes were identified.
Conclusions:
- Oncogenic proteins, such as HER-2/neu, are viable targets for cancer immunotherapy.
- Targeting these proteins may not induce destructive autoimmunity.
- Identification of epitopes can lead to tumor-specific T cell generation and peptide vaccines.