Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity

Keith L. Knutson, Kathy Schiffman, Martin A. Cheever, Mary L. Disis

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Abstract

Ideally, vaccines should be designed to elicit long-lived immunity. The goal of this study was to determine whether HER-2/neu peptide-specific CD8+ T-cell immunity could be elicited using an immunodominant HER-2/neu-derived HLA-A2 peptide alone in the absence of exogenous help. Granulocyte macrophage colony-stimulating factor (GM-CSF) was used as adjuvant. Six HLA-A2 patients with HER-2/neu-overexpressing cancers received 6 monthly vaccinations with a vaccine preparation consisting of 500 μg of HER-2/neu peptide, p369-377, admixed with 100 μg of GM-CSF. The patients had either stage III or IV breast or ovarian cancer. Immune responses to the p369-377 were examined using an IFN-γ enzyme-linked immunosorbent spot assay. Before vaccination, the median precursor frequency (range), defined as precursors per 106 peripheral blood mononuclear cell, to p369-377 was 0 (no range). After vaccination, the median precursor frequency to p369-377 in four evaluable patients was 0 (0-116). Overall, HER-2/neu peptide-specific precursors developed to p369-377 in two of four evaluable subjects. The responses were short-lived and not detectable at 5 months after the final vaccination. Immunocompetence was evident, because patients had detectable enzyme-linked immunosorbent spot responses to tetanus toxoid and influenza. These results demonstrate that HER-2/neu MHC class I epitopes can induce HER-2/neu peptide-specific IFN-γ-producing CD8+ T cells. However, the magnitude of the responses were low, as well as shortlived, suggesting that CD4+ T-cell help is required for lasting immunity to this epitope.

Original languageEnglish (US)
Pages (from-to)1014-1018
Number of pages5
JournalClinical Cancer Research
Volume8
Issue number5
StatePublished - May 27 2002

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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