Ii-Key/HER-2/neu(776-790) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER-2/neu+ tumors.

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(776-790) 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-gamma-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(435-443) CTL epitope, as illustrated by either IFN-gamma ELISPOT assays or specific autologous tumor cell lysis. Hybrid peptide-specific CD4+ T cells strongly enhanced the antitumor efficacy of HER-2/neu(435-443) 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(776-790) 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(776-790) hybrid peptides.

• Authors: 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
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 56 Issue 5 Pg. 601-13 (May 2007) ISSN: 0340-7004 [Print] Germany
• PMID: 16960693 (Publication Type: Journal Article)

Chemical References

• Antigens, Differentiation, B-Lymphocyte
• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class II
• Peptide Fragments
• Recombinant Proteins
• invariant chain
• Receptor, ErbB-2

Topics

• Antigen Presentation (immunology)
• Antigens, Differentiation, B-Lymphocyte (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Cell Line, Tumor
• Dendritic Cells (immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes, T-Lymphocyte (immunology)
• Female
• Histocompatibility Antigens Class II (immunology)
• Humans
• Lymphocyte Activation (immunology)
• Peptide Fragments (immunology)
• Receptor, ErbB-2 (immunology)
• Recombinant Proteins (immunology)
• T-Lymphocyte Subsets (immunology)