Immunization with a HER-2/neu helper peptide generates HER-2/neu CD8 T-cell immunity in cancer patients

CD4 T-cell help is required during the generation and maintenance of effect ive antitumor CD8 T cell-mediated immunity. The goal of this study was to d etermine whether HER-2/neu-specific CD8 T-cell immunity could be elicited u sing HER-2/neu-derived MHC class II "helper" peptides, which contain encomp assed HLA-A2-binding motifs. Nineteen HLA-A2 patients with HER-2/neu-overex pressing cancers received a vaccine preparation consisting of putative HER- 2/neu helper peptides p369-384, p688-703, and p971-984. Contained within th ese sequences are the HLA-A2-binding motifs p369-377, p689-697, and p971-97 9. After vaccination, the mean peptide-specific T-cell pre cursor frequency to the HLA-A2 peptides increased in the majority of patients. In addition, the peptide-specific T cells were able to lyse tumors. The responses were long lived and detectable for more than 1 year after the final vaccination in select patients. These results demonstrate that HER-2/neu MHC class II e pitopes containing encompassed MHC class I epitopes are able to induce long -lasting HER-2-specific IFN-gamma -producing CD8 T cells.