Abstract 3295: Inhibiting vascular morphogenesis in tumors: EGFL7 as a novel therapeutic target

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL EGFL7 is a vascular restricted extracellular matrix protein that is up-regulated during angiogenesis (Campagnolo et al., 2005; Fitch et al., 2004; Parker et al., 2004; Soncin et al., 2003). EGFL7 supports endothelial cell adhesion (Parker et al., 2004; Schmidt et al., 2007) and protects endothelial cells from stress-induced apoptosis (Xu et al., 2008). Inhibition of Egfl7 expression in zebrafish embryos abolished vascular lumen formation and reduced sprouting angiogenesis (Parker et al., 2004). We developed a panel of anti-EGFL7 monoclonal antibodies that block the adhesive and pro-survival activities of EGFL7. Anti-EGFL7 in combination with anti-VEGF resulted in significant tumor regression in multiple murine xenograft models, whereas anti-VEGF alone only slowed tumor growth in the same models. Anti-EGFL7 monoclonal antibodies also demonstrated prolonged survival and anti-tumor angiogenesis effects in stringent murine genetic tumor models when used as a single agent, and enhancement of anti-VEGF therapy in the combination setting. An ongoing Phase I study is being conducted to evaluate clinical safety, PK, PD and efficacy of anti-EGFL7. References: Campagnolo, L., Leahy, A., Chitnis, S., et al. EGFL7 is a chemoattractant for endothelial cells and is up-regulated in angiogenesis and arterial injury. Am J Pathol (2005) 167, 275-284. Fitch, M. J., Campagnolo, L., Kuhnert, F., et al. Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial cells. Dev Dyn (2004) 230, 316-324. Parker, L. H., Schmidt, M., Jin, S. W., et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature (2004) 428, 754-758. Schmidt, M., Paes, K., De Maziere, et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development (2007) 134, 2913-2923. Soncin, F., Mattot, V., Lionneton, F., et al. VE-statin, an endothelial repressor of smooth muscle cell migration. Embo J (2003) 22, 5700-5711. Xu, D., Perez, R. E., Ekekezie, I., et al. Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxiainduced cell death. Am J Physiol Lung Cell Mol Physiol (2008) 294, L17-L23. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3295. doi:10.1158/1538-7445.AM2011-3295