Breast Cancer Peptide Epitopes Presented by HLA-A*0201 (48.6)

Abstract

Abstract Cellular immune mechanisms detect and destroy cancerous and infected cells via the human leukocyte antigen (HLA) class I molecules that present peptides of intracellular origin on the surface of all nucleated cells. The identification of novel, tumor-specific epitopes is a critical step in the development of TCR mediated immunotherapeutics. In order to directly identify peptide epitopes unique to cancerous cells, secreted human class I HLA molecules were constructed by deletion of the transmembrane and cytoplasmic domain of HLA A*0201. The resulting sHLA-A*0201 was transferred and expressed in breast cancer cell lines MCF-7, MDA-MB-231, and BT-20 as well as in the immortal, non-tumorigenic cell line MCF10A. Stable transfectants producing sHLA-A*0201 were seeded into Bioreactors for production of > 25 mg of sHLA-A*0201. Peptides eluted from affinity purified sHLA were analyzed by mass spectroscopy and peptides derived from proteins with reported cancer association have been identified; BAP31, Cytokeratin 19, KIAA0336, and UGT1 peptide epitopes have been found on cancer cells. The identification of peptides unique to the class I of cancerous breast cells provides putative targets for immune diagnostics and therapeutics. OH is supported by NSF Graduate Fellowship 2006036207