Maximizing Immune Response to Carbohydrate Antigens on Breast Tumors
Final rept. 15 Jul 2001-14 Jul 2005
ARKANSAS UNIV FOR MEDICAL SCIENCES LITTLE ROCK
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Future progress to improve the overall survival of breast cancer patients will depend on introducing new therapies such as cancer vaccines. Because the majority of cell proteins and lipids are glycosylated, tumor associated carbohydrate antigens TACA are attractive as potential targets for cancer vaccines. However, tumor-associated carbohydrate antigens are both T-cell-independent antigens and self-antigens, impacting on their ability to induce generate strong, sustained responses against these antigens. To maximize tumor- protective immunity directed to TACA we have identified and characterized a number of peptides that mimic carbohydrate structures associated with human breast adenocarcinoma cells. Our accomplishments include 1 The induction of T cells that target naturally processed glycopeptides expressed on murine models of breast cancer 2 Showed that these mimotopes can inhibit metastatic outgrowth in these models 3 that the mimotopes can induce carbohydrate reactive antibodies that trigger apoptosis of human breast cancer cell lines 4 that these peptides can cross-react with sera from breast cancer patients that have reactivity with the carbohydrate antigen. 5 Our in vivo studies demonstrate that the peptide mimotopes induce sustained immunity to these antigens. Collectively, these data provide the experimental foundation for evaluating peptide mimotopes as potential cancer vaccines in patients with breast cancer.
- Anatomy and Physiology