The Immunogenicity and Immunoprotection of VBP3 Multi-epitope Vaccine Targeting Angiogenesis and Tumor Inhibition in Lung Cancer-Bearing Mice

Abstract

The proangiogenic factors including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) which work synergistically are essential for tumor angiogenesis and tumor growth. The bFGF/VEGF multi-epitope complex peptide (VBP3) was constructed with six different epitope peptides from human bFGF and VEGF. The VBP3 multi-epitope complex peptide was demonstrated good immunogenicity to elicit high titer anti-bFGF antibody and anti-VEGF antibody in C57BL/6 mice. In Lewis lung cancer (LLC) mouse model, the tumor growth was significantly inhibited which resulted in a longer survival time. The immunohistochemistry results showed that the tumor angiogenesis was inhibited with VBP3 vaccine vaccination. The results of flow cytometry (FCM) assay showed that the activation of dentritic cells (DC), CD4+ and CD8+ T cells were stimulated while the infiltration of myeloid-derived suppressor cells and macrophages were suppressed in tumor microenvironment. The polyclonal antibodies were separated from the VBP3-vaccinated mice. The CCK-8 assay results showed that the proliferation of LL-2 cancer cells was inhibited and the Western-blot assay results showed that the phosphorylation levels of Akt and Erk1/2 were decreased by the antibodies. The results indicated that the VBP3 could stimulate specific immune responses to inhibit tumor angiogenesis and tumor growth. The VBP3 with good immunogenicity and immunoprotection could be used as a potential therapeutic peptide vaccine for tumor therapy.