Accession Number : ADA319937

Title :   Immunogenic Structural Features of a Breast Tumor-Specific Epitope for Cancer Immunotherapy.

Descriptive Note : Annual rept. 1 Sep 95-31 Aug 96,

Corporate Author : HARRINGTON REGIONAL MEDICAL CENTER AMARILLO TX

Personal Author(s) : Dombrowski, Kenneth E.

PDF Url : ADA319937

Report Date : SEP 1996

Pagination or Media Count : 24

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.

Descriptors :   *T LYMPHOCYTES, *MAMMARY GLANDS, *IMMUNOGENS, *BREAST CANCER, NUCLEAR MAGNETIC RESONANCE, STRUCTURAL PROPERTIES, PEPTIDES, PROTEINS, NEOPLASMS, MUTATIONS, CYTOTOXINS, CELLS(BIOLOGY), CARBOHYDRATES, IMMUNIZATION, VACCINES, SUGARS, MUCIN.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE