Cancer Immunology, Immunotherapy

, Volume 56, Issue 5, pp 601–613

Ii-Key/HER-2/neu(776-90) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER-2/neu+ tumors

  • Nectaria N. Sotiriadou
  • Nikoletta L. Kallinteris
  • Angelos D. Gritzapis
  • Ioannis F. Voutsas
  • Michael Papamichail
  • Eric von Hofe
  • Robert E. Humphreys
  • Theodoros Pavlis
  • Sonia A. Perez
  • Constantin N. Baxevanis
Original Article

Abstract

We have demonstrated that coupling an immunoregulatory segment of the MHC class II-associated invariant chain (Ii), the Ii-Key peptide, to a promiscuous MHC class II epitope significantly enhances its presentation to CD4+ T cells. Here, a series of homologous Ii-Key/HER-2/neu(776-90) hybrid peptides, varying systematically in the length of the epitope(s)-containing segment, are significantly more potent than the native peptide in assays using T cells from patients with various types of tumors overexpressing HER-2/neu. In particular, priming normal donor and patient PBMCs with Ii-Key hybrid peptides enhances recognition of the native peptide either pulsed onto autologous dendritic cells (DCs) or naturally presented by IFN-γ-treated autologous tumor cells. Moreover, patient-derived CD4+ T cells primed with the hybrid peptides provide a significantly stronger helper effect to autologous CD8+ T cells specific for the HER-2/neu(435-43) CTL epitope, as illustrated by either IFN-γ ELISPOT assays or specific autologous tumor cell lysis. Hybrid peptide-specific CD4+ T cells strongly enhanced the antitumor efficacy of HER-2/neu(435-43) peptide-specific CTL in the therapy of xenografted SCID mice inoculated with HER-2/neu overexpressing human tumor cell lines. Our data indicate that the promiscuously presented vaccine peptide HER-2/neu(776-90) is amenable to Ii-Key-enhancing effects and supports the therapeutic potential of vaccinating patients with HER-2/neu+ tumors with such Ii-Key/HER-2/neu(776-90) hybrid peptides.

Keywords

Ii-Key hybrid peptides HER-2/neu peptides Cancer vaccines T helper cells CTL 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Nectaria N. Sotiriadou
    • 1
  • Nikoletta L. Kallinteris
    • 2
  • Angelos D. Gritzapis
    • 1
  • Ioannis F. Voutsas
    • 1
  • Michael Papamichail
    • 1
  • Eric von Hofe
    • 2
  • Robert E. Humphreys
    • 2
  • Theodoros Pavlis
    • 3
  • Sonia A. Perez
    • 1
  • Constantin N. Baxevanis
    • 1
  1. 1.Cancer Immunology and Immunotherapy CenterSaint Savas Cancer HospitalAthensGreece
  2. 2.Antigen Express Inc.WorcesterUSA
  3. 3.Surgical Clinic “Mitera-HospitalMarousiGreece

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