Development of novel DNA vaccine for VEGF in murine cancer model.
Development of novel DNA vaccine for VEGF in murine cancer model.
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DOI：
10.1038/srep03380
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发表时间：
2013-11-29
影响因子：
4.6
通讯作者：
Morishita, Ryuichi
中科院分区：
文献类型：
--
作者：
Kyutoku, Mariko;Nakagami, Hironori;Koriyama, Hiroshi;Tomioka, Hideki;Nakagami, Futoshi;Shimamura, Munehisa;Kurinami, Hitomi;Zhengda, Pang;Jo, Dong Hyun;Kim, Jeong Hun;Takakura, Nobuyuki;Morishita, Ryuichi
我们开发了血管内皮生长因子（VEGF）的DNA疫苗，这可能提供替代抗VEGF抗体贝伐单抗的治疗选择。以B型肝炎核心蛋白（HBc-VEGF）的B细胞表位为表位载体，构建了含VEGF微基因的质粒。用HBc-VEGF电激免疫BALB/c小鼠，可产生高滴度的抗VEGF抗体。在接种结肠26细胞的小鼠中，HBc-VEGF的肿瘤体积和微血管密度降低，生存期显著延长。从免疫小鼠纯化的IgG与HBc-VEGF的共处理显示出体外中和活性，VEGF诱导的ERK磷酸化和培养的内皮细胞中的管形成。此外，玻璃体内注射这种纯化的IgG减少了小鼠氧诱导的视网膜病变和激光诱导的脉络膜新生血管模型中的新生血管形成。这些结果首次表明VEGF DNA疫苗具有抗血管生成的作用，从而延长了小鼠肿瘤模型的生存期。
We developed DNA vaccine for vascular endothelial growth factor (VEGF), which may provide the therapeutic option instead of anti-VEGF antibody, bevacizumab. Plasmid containing VEGF mini-gene was constructed in the insertion of B-cell epitope of Hepatitis B core protein [HBc-VEGF], which was an epitope carrier. High titer of anti-VEGF antibody was observed in BALB/c mice which were intramuscularly immunized with HBc-VEGF by electropolator. In mice inoculated with colon 26 cells, tumor volume and microvessel density was decreased in HBc-VEGF with a significant prolonged survival. Co-treatment of purified IgG from immunized mice with HBc-VEGF showed in vitro neutralizing activity for VEGF-induced ERK phosphorylation and tube formation in cultured endothelial cells. Furthermore, intravitreally injection of this purified IgG reduced the neovessel formation in the mouse oxygen-induced retinopathy and laser-induced choroidal neovascularization models. These results first provided that DNA vaccine against VEGF possessed the anti-angiogenic effect, leading to prolonged survival in mouse cancer model.
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