Angiogenesis Inhibition Mediated by VBP3 Complex Peptide Vaccine and Immunoprotection of Lewis Lung Carcinoma-Bearing Mice
Angiogenesis Inhibition Mediated by VBP3 Complex Peptide Vaccine and Immunoprotection of Lewis Lung Carcinoma-Bearing Mice
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VBP3复合肽疫苗介导的血管生成抑制及Lewis肺癌荷瘤小鼠的免疫保护
DOI：
10.1007/s10989-017-9667-4
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发表时间：
2017
影响因子：
2.5
通讯作者：
Ning Deng
中科院分区：
文献类型：
--
作者：
Ligang Zhang;Yanrui Deng;Ruiqiang Weng;Lei Pan;Ning Deng
促血管生成因子包括碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF），它们协同作用对肿瘤血管生成和肿瘤生长至关重要。利用人bFGF和VEGF的6个不同表位肽构建了bFGF/VEGF多表位复合肽（VBP 3）。VBP 3多表位复合肽在C57 BL/6小鼠体内具有良好的免疫原性，可诱导产生高效价的抗bFGF抗体和抗VEGF抗体。在刘易斯肺癌（LLC）小鼠模型中，肿瘤生长受到明显抑制，存活时间延长。免疫组化结果显示，VBP 3疫苗接种可抑制肿瘤血管生成。流式细胞术（FCM）检测结果显示，肿瘤微环境中树突状细胞（DC）、CD 4+和CD 8 +T细胞的活化被激活，髓源性抑制细胞和巨噬细胞的浸润被抑制。从接种VBP 3的小鼠分离多克隆抗体。CCK-8检测结果显示抗体对LL-2细胞的增殖有抑制作用，Western-blot检测结果显示抗体可降低Akt和Erk 1/2的磷酸化水平。结果表明，VBP 3能刺激特异性免疫反应，抑制肿瘤血管生成和肿瘤生长。VBP 3具有良好的免疫原性和免疫保护性，可作为一种潜在的治疗性肽疫苗用于肿瘤治疗。
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.