TY - JOUR
T1 - Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity
AU - Knutson, Keith L.
AU - Schiffman, Kathy
AU - Cheever, Martin A.
AU - Disis, Mary L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036098003&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036098003&partnerID=8YFLogxK
M3 - Article
C2 - 12006513
AN - SCOPUS:0036098003
SN - 1078-0432
VL - 8
SP - 1014
EP - 1018
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -