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Publication : A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth.

First Author  Holmgren L Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  24 Pages  9208-13
PubMed ID  16754857 Mgi Jnum  J:111046
Mgi Id  MGI:3652656 Doi  10.1073/pnas.0603110103
Citation  Holmgren L, et al. (2006) A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. Proc Natl Acad Sci U S A 103(24):9208-13
abstractText  Endogenous angiogenesis inhibitors have shown promise in preclinical trials, but clinical use has been hindered by low half-life in circulation and high production costs. Here, we describe a strategy that targets the angiostatin receptor angiomotin (Amot) by DNA vaccination. The vaccination procedure generated antibodies that detected Amot on the endothelial cell surface. Purified Ig bound to the endothelial cell membrane and inhibited endothelial cell migration. In vivo, DNA vaccination blocked angiogenesis in the matrigel plug assay and prevented growth of transplanted tumors for up to 150 days. We further demonstrate that a combination of DNA vaccines encoding Amot and the extracellular and transmembrane domains of the human EGF receptor 2 (Her-2)/neu oncogene inhibited breast cancer progression and impaired tumor vascularization in Her-2/neu transgenic mice. No toxicity or impairment of normal blood vessels could be detected. This work shows that DNA vaccination targeting Amot may be used to mimic the effect of angiostatin.
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