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 (IC 50 50 435 ), HER2(9 665 ), HER2(9 689 ), and HER2(10 952 ), and confirm that of the known HER2 (9 369 ) epitope. These epitopes were able to elicit CTL 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 (9 369 ), HER2(9 435 ), and HER2(9 689 ) epitopes. Finally, CTL clones specific for HER2 (9 369 ), HER2(9 435 ), and HER2(9 689 ) 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.