Proliferative and cytokine responses to class II HER-2/neuassociated peptides in breast cancer patients

Todd M. Tuttle, Brett W. Anderson, William E. Thompson, Jeffrey E. Lee, Aysegul Sahin, Terry L. Smith, Kenneth H. Grabstein, J. Taylor Wharton, Constantin G. Ioannides, James L. Murray

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53 Scopus citations

Abstract

Previous studies have characterized the reactivity of CD8+ CTLs with ovarian and breast cancer. There is little information about the antigens and epitopes recognized by CD4+ T cells in these patients. In this study, we analyzed the ability of T cells from peripheral blood mononuclear cells of breast cancer patients to recognize HER-2/neu (HER-2) peptides. We found that 13 of 18 patients responded by proliferation to at least one of the HER-2 peptides tested. Of these peptides, one designated G89 (HER-2: 777-789) was recognized by T cells from 10 patients. Seven of nine responding patients were HLA-DR4+, suggesting that this peptide is recognized preferentially in association with HLA-DR4. Analysis of the specificity and restriction of the cytokine responses to G89 by G89-stimulated T cells revealed that these cells secreted significantly higher levels of IFN-γ than interleukin 4 and interleukin 10, suggesting priming for a Th0-T helper 1 response. The same pattern of cytokine responses was observed to the intracellular domain of HER-2 protein, suggesting that G89-stimulated T cells recognized epitopes of the HER-2 protein in association with HLA-DR4. Because HLA-DR4 is present in 25% of humans, characterization of MHC class H-restricted epitopes inducing Th0-T helper 1 responses may provide a basis for the development of multivalent HER-2-based vaccines against breast and ovarian cancer.

Original languageEnglish (US)
Pages (from-to)2015-2024
Number of pages10
JournalClinical Cancer Research
Volume4
Issue number8
StatePublished - Aug 1998

Bibliographical note

Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.

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