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01-05-2010 | Original Article

Identification and characterization of a HER-2/neu epitope as a potential target for cancer immunotherapy

Authors: Eftychia Lekka, Angelos D. Gritzapis, Sonia A. Perez, Nikolaos Tsavaris, Ioannis Missitzis, Avgi Mamalaki, Michael Papamichail, Constantin N. Baxevanis

Published in: Cancer Immunology, Immunotherapy | Issue 5/2010

Abstract

Our aim is to develop peptide vaccines that stimulate tumor antigen-specific T-lymphocyte responses against frequently detected cancers. We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828–836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu ⁺ tumor cell lines. HER-2/neu(828-836), [HER-2(9₈₂₈)], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay. This peptide was stable for 3.5 h in an off-kinetic assay. HER-2(9₈₂₈) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity. Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8⁺ T-lymphocytes specifically recognizing HER-2(9₈₂₈) in 8 out of 20 HLA-A*0201⁺ HER-2/neu ⁺ breast cancer patients. Moreover, HER-2(9₈₂₈)-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201. Finally, therapeutic vaccination with HER-2(9₈₂₈) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice. Our data encourage further exploitation of HER-2(9₈₂₈) as a promising candidate for peptide-based cancer vaccines.

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Title: Identification and characterization of a HER-2/neu epitope as a potential target for cancer immunotherapy
Authors: Eftychia Lekka
Angelos D. Gritzapis
Sonia A. Perez
Nikolaos Tsavaris
Ioannis Missitzis
Avgi Mamalaki
Michael Papamichail
Constantin N. Baxevanis
Publication date: 01-05-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 5/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0791-7

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