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Vaccine. 2009 Dec 10;28(1):162-70. doi: 10.1016/j.vaccine.2009.09.104. Epub 2009 Sep 30.

HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties.

Author information

1
Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Athens, Greece.

Abstract

The HER-2/neu oncoprotein is a promising cancer vaccine target. We describe herein a novel HLA-A2.1-restricted epitope, encompassing amino acids 657-665 (AVVGILLVV), which is naturally presented by human breast and ovarian cell lines. HER-2/neu(657-665), [HER-2(9(657))], binds with high affinity to HLA-A2.1 molecules as revealed by a prediction algorithm (SYFPEITHI) and in functional assays. This peptide was found to be immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded with increased IFNgamma production, degranulation, and in vitro as well as in vivo cytotoxicity. Most important, HER-2(9(657)) functioned as a therapeutic vaccine by enabling HHD mice to reject established transplantable tumors. Cured mice resisted tumor growth when re-challenged with the same tumor, demonstrating the capacity of HER-2(9(657)) to generate tumor-specific memory immune response. Finally, this peptide was also found to be immunogenic in PBMCs from HLA-A2.1(+) patients with HER-2/neu(+) breast cancer. Our data encourage further exploitation of HER-2(9(657)) as a promising candidate for peptide-based cancer vaccines.

PMID:
19799847
DOI:
10.1016/j.vaccine.2009.09.104
[Indexed for MEDLINE]

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