Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas

Twenty-two new HLA-A2. 1-binding peptides derived from the protooncogene HER2/neu were identified and analyzed for their capacity to elicit peptide and tumor-specific CTL responses. We used peptide-pulsed autologous DC from the ascites of patients with ovarian carcinomas to induce CTL. Of the 22 tested new HER2/neu-derived epitopes that could bind HLA-A2 with high (IC₅₀ < 50 nM) or intermediate (50 nM< IC₅₀ < 500 nM) affinity, we report the recognition by CTL of at least four novel epitopes, including HER2(9₄₃₅), HER2(9₆₆₅), HER2(9₆₈₉), and HER2(10₉₅₂), and confirm that of the known HER2 (9₃₆₉) epitope. These epitopes were able to elicit CTI, that specifically killed peptide-sensitized target cells and, most importantly, a HER2/neu-transfected cell line and the autologous tumor cells. We also confirm that HER2/neu is overexpressed in several melanoma lines, and as a new finding, report that some of these lines are sensitive to CTL induced by the HER2 (9₃₆₉), HER2(9₄₃₅), and HER2(9₆₈₉) epitopes. Finally, CTL clones specific for HER2 (9₃₆₉), HER2(9₄₃₅), and HER2(9₆₈₉) epitopes were isolated from tumor-specific CTL lines, further demonstrating the immunodominance of these epitopes. These findings broaden the potential application of HER2/neu-based immunotherapy.