HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties.
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.
Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Athens, Greece.
Angelos D
AD
Gritzapis
Arthur
A
Fridman
Sonia A
SA
Perez
Nicola
N
La Monica
Michael
M
Papamichail
Luigi
L
Aurisicchio
Constantin N
CN
Baxevanis
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases