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Cancer Immunology, Immunotherapy

, Volume 59, Issue 5, pp 715–727 | Cite as

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

  • Eftychia LekkaEmail author
  • Angelos D. Gritzapis
  • Sonia A. Perez
  • Nikolaos Tsavaris
  • Ioannis Missitzis
  • Avgi Mamalaki
  • Michael Papamichail
  • Constantin N. Baxevanis
Original Article

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.

Keywords

HER-2/neu Peptide vaccines HHD mice CTL Breast cancer 

Notes

Acknowledgments

This work was supported by grants from the General Secretariat of Research and Technology EPAN YB/3 and PENED 03ED113 (to C.N.B.), and from Regional Operational Program Attika No. 20; MIS code 59605 GR (to M.P.) The authors have no financial conflict of interest.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Eftychia Lekka
    • 1
    Email author
  • Angelos D. Gritzapis
    • 1
  • Sonia A. Perez
    • 1
  • Nikolaos Tsavaris
    • 2
  • Ioannis Missitzis
    • 3
  • Avgi Mamalaki
    • 4
  • Michael Papamichail
    • 1
  • Constantin N. Baxevanis
    • 1
  1. 1.Cancer Immunology and Immunotherapy CenterSaint Savas Cancer HospitalAthensGreece
  2. 2.Pathophysiology Department, Laikon General Hospital and Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.Breast Cancer ClinicSaint Savas Cancer HospitalAthensGreece
  4. 4.Laboratory of Molecular Biology and Immunobiotechnology, Department of BiochemistryHellenic Pasteur InstituteAthensGreece

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