Immunogenic Structural Features of a Breast Tumor-Specific Epitope for Cancer Immunotherapy.
Abstract
The objectives of the research program are to study the structure-immunogenicity relationships of a hypoglycosylated human tumor-specific mucin common to breast and other adenocarcinomas. Hypoglycosylation of breast mucin leads to exposure of a tumor-specific epitope (TSE). The structural and immunogenic properties of the TSE are being examined using synthetic mucin peptides and recombinant mucin proteins that contain the TSE and/or mutations in potential glycosylation sites surrounding the TSE. A single 20 amino acid tandem repeat of mucin is immunogenic. It stimulates the production of polyclonal antibodies and tumor-specific cytotoxic T lymphocytes. The single tandem repeat peptide was shown to contain few elements of preferred conformation, based on 1H-NMR spectroscopy. A model of the distribution of the oligosaccharide side chains along the mucin core protein was developed showing that the carbohydrates may not surround the protein in a uniform "coating". Thus, regions of the core protein are exposed under normal circumstances, yet tumor-specific epitopes remain masked by the sugars in the non-malignant cells. Further understanding of the structure-immunogenicity relationships of tumor-specific immunogens is essential for maximizing the use of synthetic peptide immunogens and tumor-specific cells as a potential adoptive immunotherapy for patients with cancer, and the development of a potential vaccine.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1996
- Accession Number
- ADA319937
Entities
People
- Kenneth E. Dombrowski