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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Immunization with a HSP65-HER2 fusion peptide selectively eliminates HER2(+) B16 melanoma cells in a xenograft tumor
Junying Wang1, Xueju Wang, Yajing Chen
1Department of Immunology, Medical College of Norman Bethune, Jilin University, Changchun, 130021, China. wangjunyingjilin@163.com
Abstract:
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.
Insights
A novel HSP65-HER2 fusion peptide vaccine effectively reduced tumor incidence and HER2(+) B16 melanoma cell percentages in mice. This targeted therapy shows promise for HER2/neu(+) tumors.
Area of Science:
- Immunology
- Oncology
- Vaccine Development
Background:
- HER2/neu peptide vaccines show suboptimal efficacy against HER2/neu-overexpressing tumors.
- Heat shock proteins (HSPs) can elicit potent cytotoxic T lymphocyte (CTL) responses via cross-presentation.
- Developing enhanced strategies to target HER2/neu(+) cancers is crucial.
Purpose of the Study:
- To evaluate the efficacy of a HSP65-HER2 fusion peptide immunization in a xenograft mouse model.
- To determine if HSP65-HER2 fusion peptide can selectively eliminate HER2(+) B16 melanoma cells.
- To assess the immunomodulatory effects of the HSP65-HER2 fusion peptide.
Main Methods:
- In vitro incubation of immature dendritic cells (iDCs) with HSP65-HER2 to assess CD86 expression.
- In vivo immunization of mice with HSP65-HER2 or PBS, monitoring tumor volume, weight, and incidence.
- Confocal microscopy and flow cytometry to quantify HER2(+) B16 cell percentages in tumors.
Main Results:
- HSP65-HER2 loading on iDCs induced CD86 expression, indicating immune response stimulation.
- Immunization with HSP65-HER2 significantly reduced tumor incidence (62.5% vs. 100% in controls).
- HSP65-HER2 immunization significantly decreased HER2(+) B16 cell percentages in tumors (1.86% vs. 30.56% in controls).
Conclusions:
- The HSP65-HER2 fusion peptide selectively eliminates HER2(+) B16 melanoma cells in a xenograft model.
- This fusion peptide represents a potential novel and effective targeted therapy for HER2/neu(+) tumors.
- Further research into HSP-based fusion peptide vaccines is warranted for cancer treatment.

