Immunization with a HSP65–HER2 fusion peptide selectively eliminates HER2+ B16 melanoma cells in a xenograft tumor mouse model
HER2/neu peptide-based vaccines can eliminate human tumors overexpressing the human epidermal growth factor receptor 2 (HER2/neu), but the efficacy of this therapeutic strategy is suboptimal. Heat shock proteins (HSPs) are capable of eliciting efficient cytotoxic T lymphocyte (CTL) responses by cross-presentation. To evaluate whether immunization with a HSP65–HER2 fusion peptide could selectively eliminate HER2+ B16 melanoma cells in a xenograft tumor mouse model, a HSP65–HER2 fusion peptide was incubated with immature dendritic cells (iDCs) in vitro to determine whether loading of iDCs with HSP65–HER2 could induce the expression of the immunomodulatory cell surface molecule, CD86. In vivo mouse immunizations with HSP65–HER2 or PBS (control) were performed to determine the antitumor effects by longitudinally monitoring changes in tumor volume, weight, and incidence. The effects on percentages of HER2+ B16 cells in tumors were assessed by confocal microscopy and flow cytometry. The results indicated that loading of iDCs with HSP65–HER2 induced the expression of CD86 in vitro, suggesting that the hybrid antigen was able to stimulate an immune response. Immunization with HSP65–HER2 had no significant influence on tumor weight or volume but significantly reduced tumor incidence (62.5 % in mice injected with 25 μg of HSP65–HER2 vs. 100 % in PBS-injected controls; P < 0.05). Confocal microscopy and flow cytometry analyses revealed that HSP65–HER2 immunization significantly reduced the percentages of HER2+ B16 cells in xenografted tumors (1.86 % vs. 30.56 % in PBS-injected controls; P = 0.01). Our findings suggest that immunization with the HSP65–HER2 fusion peptide selectively eliminates HER2+ B16 melanoma cells in a xenograft tumor mouse model and may represent a novel and efficacious targeted therapy of HER2/neu+ tumors.
KeywordsHER2 HSP65 Tumor vaccine Immunization Epitope
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