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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 distibution 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.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Aug 95-31 Jul 96 |
| Pages: |
23 |
| Report Date: |
AUG 96 |
| Contract Number: |
DAMD17-94-J-4161 |
| Report Number: |
A194713 |
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