Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients.
CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell-mediated immunity. The goal of this study was to determine whether HER-2/neu-specific CD8 T-cell immunity could be elicited using HER-2/neu-derived MHC class II "helper" peptides, which contain encompassed HLA-A2-binding motifs. Nineteen HLA-A2 patients with HER-2/neu-overexpressing cancers received a vaccine preparation consisting of putative HER-2/neu helper peptides p369-384, p688-703, and p971-984. Contained within these sequences are the HLA-A2-binding motifs p369-377, p689-697, and p971-979. After vaccination, the mean peptide-specific T-cell precursor 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 epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2-specific IFN-gamma-producing CD8 T cells.
Knutson
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KL
Division of Oncology, University of Washington, 1959 NE Pacific Street, Health Sciences Building BB1361, Seattle, WA 98195-6527, USA. kknutson@u.washington.edu
Schiffman
K
K
Disis
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ML
D000328:Adult; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014611:Vaccination
D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases