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her2/neu-derived peptide epitopes month download article/chapter mhc class ii peptide-based vaccines hybrid peptide-specific cd4+ ii-key-enhancing effects human leukocyte antigen-dr1 melanoma-specific cytolytic cd8+ human tumor-reactive cd4+ lopez-diaz de cerio ny-eso-1 epitopes presented human tumor-specific ctls ifn-γ elispot assays ny-eso-1-expressing melanoma vitro-induced specific cd4 major “post-licensing-role g89-activated cells regulate cytotoxic-t-cell responses related subjects ii-key peptide mhc class human histocompatibility antigen 2/neu-derived peptide 884-99 high-affinity p53a2 article cancer immunology peptide her2 full article pdf antigen-specific cd4+ tumor-specific cd4+ tumor antigen-specific hybrid peptide linking homologous ii-key/ peptide-specific ctl effective immunological responses cd4+ t-helper t-killer cell helper peptide g89 tumor-derived helper patient-derived cd4+ privacy choices/manage cookies human primary breast eric von hofe & robert tumor cell vaccine quantify antigen-specific human tumor antigens ii-key segment class ii peptide-specific cytotoxic knutson kl tumor specific cytolysis

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         description: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.
         datePublished:2006-09-08T00:00:00Z
         dateModified:2006-09-08T00:00:00Z
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            Immunology
            Cancer Research
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      headline: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
      description: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.
      datePublished:2006-09-08T00:00:00Z
      dateModified:2006-09-08T00:00:00Z
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         Ii-Key hybrid peptides
         HER-2/neu peptides
         Cancer vaccines
         T helper cells
         CTL
         Oncology
         Immunology
         Cancer Research
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