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首页> 外文期刊>BMC Biotechnology >Mimotope vaccination for epitope-specific induction of anti-VEGF antibodies
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Mimotope vaccination for epitope-specific induction of anti-VEGF antibodies

机译：模拟表位疫苗可诱导抗原表位特异性诱导抗VEGF抗体

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Background Tumor angiogenesis is critical for tumor growth, infiltration and metastasis. Vascular endothelial growth factor ( VEGF ) is a potent angiogenic factor and targeting it is important in reducing angiogenesis. Bevacizumab ( Avastin ), a monoclonal antibody that reacts directly against VEGF , has been demonstrated to be an effective treatment for various cancers such as rectal cancer, colon carcinoma, and non-small cell lung cancer, etc. Results In the current study, we used the phage display technique to generate mimotopes that complemented the screening Avastin antibody (Ab). The candidate mimotopes of VEGF were isolated from a 12-mer peptide library. The phage displaying peptide DHTLYTPYHTHP (designated as 12P) exhibited high affinity to Avastin . The chemically synthesized 12P was conjugated to keyhole limpet hemocyanin (KLH) by glutaraldehyde (GA) to form vaccine KLH-12 peptide (KLH-12P). This epitope vaccine significantly induced humoral immunity in mice. The blood serum from KLH-12P-immunized mice associated with VEGF and blocked its binding to VEGFR , thus inhibiting vascular endothelial cell proliferation and migration. Conclusions Our data indicate that the isolated mimotope 12P reported here could potentially elicit specific antibodies against VEGF and result in the induction of anti-angiogenesis responses.
机译：背景技术肿瘤血管生成对于肿瘤的生长，浸润和转移至关重要。血管内皮生长因子（VEGF）是有效的血管生成因子，靶向它在减少血管生成中很重要。直接对VEGF反应的单克隆抗体贝伐单抗（Avastin）已被证明是治疗各种癌症的有效方法，例如直肠癌，结肠癌和非小细胞肺癌等。结果在本研究中，我们使用噬菌体展示技术来生成模拟表位，该表位与筛选的Avastin抗体（Ab）互补。 VEGF的候选模拟表位是从12聚体肽库中分离出来的。噬菌体展示肽DHTLYTPYHTHP（指定为12P）对Avastin具有高亲和力。化学合成的12P通过戊二醛（GA）与匙孔戚血蓝蛋白（KLH）结合，形成疫苗KLH-12肽（KLH-12P）。这种表位疫苗可在小鼠中显着诱导体液免疫。来自KLH-12P免疫小鼠的血清与VEGF结合并阻断了其与VEGFR的结合，从而抑制了血管内皮细胞的增殖和迁移。结论我们的数据表明，此处报道的分离的模拟表位12P可能潜在地引发针对VEGF的特异性抗体，并诱导抗血管生成反应。

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