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

Research output: Contribution to journalArticle

190 Citations (Scopus)

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 - 2002
Externally publishedYes

Fingerprint

HLA-A2 Antigen
Immunity
Immunization
Vaccination
Peptides
Neoplasms
Granulocyte-Macrophage Colony-Stimulating Factor
T-Lymphocytes
Epitopes
Vaccines
Immunocompetence
Immunosorbents
Tetanus Toxoid
Ovarian Neoplasms
Human Influenza
Blood Cells
Enzyme-Linked Immunosorbent Assay
Breast Neoplasms
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. / Knutson, Keith L; Schiffman, Kathy; Cheever, Martin A.; Disis, Mary L.

In: Clinical Cancer Research, Vol. 8, No. 5, 2002, p. 1014-1018.

Research output: Contribution to journalArticle

@article{b363511f87ed4a6f9b0b1e538498a5a1,
title = "Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity",
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.",
author = "Knutson, {Keith L} and Kathy Schiffman and Cheever, {Martin A.} and Disis, {Mary L.}",
year = "2002",
language = "English (US)",
volume = "8",
pages = "1014--1018",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

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.

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

VL - 8

SP - 1014

EP - 1018

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 5

ER -