Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer

M. L. Disis, Keith L Knutson, K. Schiffman, K. Rinn, D. G. McNeel

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1-75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11%) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index ≥ 2.0 (range 2.0-7.9). None of eight patients who were HLA-A2 had a detectable IFNγ secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) had detectable HER-2/neu specific IgG antibodies, range 1.2-8.9 μg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalBreast Cancer Research and Treatment
Volume62
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Immunity
Breast Neoplasms
Proteins
HLA-A2 Antigen
T-Lymphocytes
Antibodies
T-Lymphoid Precursor Cells
Cancer Vaccines
T-Lymphocyte Epitopes
Residual Neoplasm
Neoplasm Antigens
Immunosuppressive Agents
Skin Tests
Antibody Formation
Neoplasms
Immunoglobulin G
Antigens
Recurrence
Drug Therapy

Keywords

  • Antibody
  • Breast cancer
  • HER-2/neu
  • Immunity
  • Ovarian cancer
  • T-cell

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. / Disis, M. L.; Knutson, Keith L; Schiffman, K.; Rinn, K.; McNeel, D. G.

In: Breast Cancer Research and Treatment, Vol. 62, No. 3, 2000, p. 245-252.

Research output: Contribution to journalArticle

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abstract = "Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1-75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11{\%}) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index ≥ 2.0 (range 2.0-7.9). None of eight patients who were HLA-A2 had a detectable IFNγ secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7{\%}) had detectable HER-2/neu specific IgG antibodies, range 1.2-8.9 μg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.",
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