Accession Number : ADA317491

Title :   Breast Mucin Tumor-Specific Epitopes for Cancer Immunotherapy.

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

Corporate Author : TEXAS TECH UNIV HEALTH SCIENCES CENTER AMARILLO

Personal Author(s) : Dombrowski, Kenneth E.

PDF Url : ADA317491

Report Date : AUG 1996

Pagination or Media Count : 23

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.

Descriptors :   *CANCER, *MUCIN, NUCLEAR MAGNETIC RESONANCE, SPECTROSCOPY, PEPTIDES, PROTEINS, NEOPLASMS, MUTATIONS, ANTIBODIES, HUMAN BODY, CYTOTOXINS, T LYMPHOCYTES, CELLS(BIOLOGY), CARBOHYDRATES, IMMUNIZATION, AMINO ACIDS, VACCINES, SUGARS, BREAST CANCER.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research
      Toxicology
      Pharmacology
      Atomic and Molecular Physics and Spectroscopy

Distribution Statement : APPROVED FOR PUBLIC RELEASE