Abstract 1363: Inhibition of Neuropilin-1 by anti-Nrp1 results in reduced angiogenesis and inhibition of tumor growth

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Neuropilin-1 (NRP1) guides the development of the nervous and vascular systems and has been implicated in modulating various aspects of tumor cell function. We have previously shown that an antibody directed against NRP1 inhibits tumor growth and reduces tumor angiogenesis, as a single agent and more potently in combination with anti-VEGF. However, as NRP1 was also expressed in the tumor cells tested, the impact from inhibiting tumor cell NRP1 in these experiments was unclear. The objective of this study was to determine if inhibition of tumor cell NRP1 was necessary for the observed anti-tumor effects previously described for anti-NRP1. We tested the effects of anti-NRP1 in tumor lines that do not express NRP1, and where expression of NRP1 is restricted to the vasculature. Inhibition of tumor growth as a single agent, and in combination with anti-VEGF in these xenografted tumor lines, confirm that tumor expression of NRP1 is not necessary for the anti-tumor effects of anti-NRP1. We furthermore demonstrate that anti-NRP1 treatment of endothelial cells in in vitro sprouting assays results in potent inhibition of vascular sprout formation, confirming its anti-angiogenic activity. In vivo, in developmental models of angiogenesis, treatment results in reduced angiogenesis that is augmented by anti-VEGF. Finally, we demonstrate that treatment of primates with anti-NRP1 results in up-regulation of cytokines, such as PlGF, that are commonly increased with anti-angiogenic agent treatment. In total, these data confirm that anti-NRP1 mechanistically acts to inhibit tumor angiogenesis, thus resulting in reduced tumor growth and this tumor inhibition is most effective in combination with VEGF inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1363.