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Saied Mirshahidi, James B Whitney, Victor G Kramer, Karen S Anderson, Ruth M Ruprecht, Using Overlapping Synthetic Peptides from Tumor-Associated Protein Antigens for Breast Cancer Vaccine Development. (41.11), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S32, https://doi.org/10.4049/jimmunol.178.Supp.41.11
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Abstract
An effective vaccine will need to elicit both CD4+ T helper and CD8+ cytotoxic T lymphocytes (CTL) responses in order to maintain effective CTL functions. Peptide vaccines tailored to certain genetic backgrounds are capable of eliciting MHC Class I-restricted (CD8+) and Class II-restricted (CD4+) responses. However, the need to identify specific T-cell epitopes in the context of MHC alleles hampers this approach. We have developed a novel strategy that bypasses the need for epitope mapping for an outbred population: vaccination with overlapping synthetic peptides (OSP), to generate strong antigen-specific cell-mediated immunity (CMI) in individual vaccine recipients with different MHC backgrounds. OSP contain all possible epitopes for the CD4+ as well as CD8+ T cells of a genetically diverse population. BALB/c mice were immunized with OSP derived from a tumor protein, which is overexpressed in 60% in breast cancer specimens. The vaccinated animals developed an in vitro activity of tumor specific- CTL, proliferative response, IFN-g production and CD107 expression. Immunized mice also were challenged with TS/A tumor cells (a murine mammary adenocarcinoma cell) to induce micrometastasis. Vaccination with OSP significantly increased the animal life span. The OSP vaccine strategy provides a novel opportunity to induce cellular immune responses against developing tumors in a genetically diverse population.
