A DNA Vaccine Targeting Angiomotin Inhibits Angiogenesis and Suppresses Tumor Growth

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Jun 7

PMID 16754857

Citations 36

Authors

Lars Holmgren

Elena Ambrosino

Olivier Birot

Carl Tullus

Niina Veitonmaki

Tetyana Levchenko

Lena-Maria Carlson

Piero Musiani

Manuela Iezzi

Claudia Curcio

Guido Forni

Federica Cavallo

Rolf Kiessling

Affiliations

Soon will be listed here.

Abstract

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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