Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library for Cancer Therapy

摘要: Vascular endothelial growth factor (VEGF) is an important stimulator for angiogenesis in solid tumors. Blocking VEGF activity effective therapeutic strategy to inhibit tumor and metastasis. Avastin, a humanized monoclonal antibody recognizes VEGF, has been approved by the US Food Drug Administration. To generate potential VEGF-recognizing antibodies with better regression ability than that of we have designed systematic selection plan. From mice immunized recombinant human generated three phage display libraries, scFv-M13KO7, Fab-M13KO7, scFv-Hyperphage, single-chain Fv (scFv) or Fab format, displayed using either M13KO7 helper Hyperphage. Solid-phase solution-phase strategies were then applied each library, generating six panning combinations. A total sixty-four recognizing obtained. Based on results epitope mapping, binding affinity, biological functions inhibition, eight chosen examine their abilities mouse xenograft model COLO 205 cancer cells. Three them showed improvement inhibition (328%–347% ratio (% Day 0 volume) 21 vs. 435% Avastin). This finding suggests use these VEGF-targeted therapy.