Abstract LB-284: The novel therapeutic monoclonal antibody VGX-100 neutralises VEGF-C and inhibits tumor growth and metastasis in subcutaneous and orthotopic models of human cancer.

Abstract

Abstract Angiogenesis and lymphangiogenesis are important processes facilitating tumor growth and metastasis. Growth factors that stimulate blood and lymphatic proliferation within tumors are therefore potential targets for anti-cancer therapies. Proof of concept of the clinical utility of anti-angiogenic drugs was first established by the FDA/EMEA-approved drug bevacizumab (Avastin®) which blocks VEGF binding to its receptors VEGFR-1 and VEGFR-2, the latter being the key receptor signaling for angiogenesis. However, patients treated with bevacizumab may be refractory or develop resistance to bevacizumab, suggesting upregulation of alternative pro-angiogenic proteins that allow tumors to bypass the inhibition of VEGF signalling. VEGF-C is a logical candidate for inducing resistance to bevacizumab via this mechanism since it is also a ligand for the angiogenic receptor VEGFR-2 and for VEGFR-3 which is upregulated on tumor-associated vascular endothelium. VGX-100 is a highly specific, fully human monoclonal antibody for VEGF-C that blocks VEGF-C binding to both VEGFR-2 and VEGFR-3. Here we demonstrate that VGX-100 has an additive effect in combination with docetaxel and/or anti-VEGF (bevacizumab) in several tumor models, suggesting that VEGF-C may be an important mediator of the resistance to existing anti-VEGF therapies. Further, we demonstrate that in an orthotopic model of prostate cancer, that inhibition of VEGF-C alone by VGX-100 monotherapy is sufficient to inhibit tumor growth and significantly reduce the incidence of tumor metastasis to local lymph nodes. These data indicate that VGX-100 has exciting potential as a cancer therapeutic by targeting a key factor involved in angiogenesis, lymphangiogenesis and tumor metastasis and is expected to complement chemotherapy and/or other anti-angiogenic compounds in the clinic. 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 LB-284. doi:10.1158/1538-7445.AM2011-LB-284