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Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2002 May; Vol. 8 (5), pp. 1014-8. - Publication Year :
- 2002
-
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 microg of HER-2/neu peptide, p369-377, admixed with 100 microg 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-gamma enzyme-linked immunosorbent spot assay. Before vaccination, the median precursor frequency (range), defined as precursors per 10(6) 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-gamma-producing CD8+ T cells. However, the magnitude of the responses were low, as well as short-lived, suggesting that CD4+ T-cell help is required for lasting immunity to this epitope.
- Subjects :
- Aged
Breast Neoplasms drug therapy
Breast Neoplasms pathology
Cancer Vaccines administration & dosage
Cancer Vaccines immunology
Drug Therapy, Combination
Female
Granulocyte-Macrophage Colony-Stimulating Factor immunology
Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use
Humans
Leukocytes, Mononuclear cytology
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear immunology
Middle Aged
Neoplasm Staging
Ovarian Neoplasms drug therapy
Ovarian Neoplasms pathology
Peptide Fragments immunology
Peptide Fragments therapeutic use
Receptor, ErbB-2 chemistry
Receptor, ErbB-2 therapeutic use
T-Lymphocytes cytology
T-Lymphocytes drug effects
T-Lymphocytes immunology
Time Factors
Treatment Outcome
Vaccination
Breast Neoplasms immunology
HLA-A2 Antigen immunology
Ovarian Neoplasms immunology
Receptor, ErbB-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 12006513