3018 Background: Vascular endothelial growth factor (VEGF) plays a central role in neoangiogenesis and thus represents an important therapeutic target in antiangiogenic cancer therapy strategies. We have developed an anti-VEGF vaccine VEGF kinoid that elicits high titres of neutralizing anti-VEGF antibodies in mice. In this study we have evaluated the immunogenicity, safety and efficacy of VEGF kinoid in preventing tumor growth and metastases in mice. Methods: The efficacy of VEGF kinoid was evaluated in a model of active immunization (CT26 colon carcicoma lung metastases model) and in two models of passive immunization. On the passive immunization setting two VEGF secreting xenograft tumor models, A673 rhabdomyosarcoma and HT29 colon carcinoma, were used to evaluate the ability of IgGs derived from kinoid immunized mice to inhibit tumor growth in comparison with bevacizumab. Results: Active immunization with autologous VEGF Kinoid (mVEGF kinoid) triggered a strong anti-VEGF antibody but no cellular immune response in mice. The anti-VEGF Abs exhibited high neutralizing capacity as assessed via inhibition of human umbilical vein endothelial cell proliferation in the presence of VEGF and binding to the Flk-1 receptor. In mVEGF kinoid immunized BALB/c mice challenged with syngeneic CT26 colorectal tumor cells the lung metastases were inhibited. In human VEGF (hVEGF) kinoid immunized Balb/c mice neutralizing anti-hVEGF Abs were elicited. Purified IgG from these mice inhibited tumor growth of human A673 rhabdomyosarcoma and HT29 colon carcinoma cells xenografted in Swiss nude and NOD/SCID mice respectively as assessed by T/C% measurements. Tumor cell growth inhibition was similar to that in mice receiving therapeutic doses of bevacizumab. Active immunization against VEGF showed an excellent safety profile in mice and no impairment of would healing processes was observed after surgical interventions in immunized mice. Conclusions: These experiments show that active immunization with VEGF kinoid elicits polyclonal neutralizing anti-VEGF Abs that inhibit metastases and tumor growth in mice. It may thus represent an alternative strategy to safely combat VEGF-dependent neovascularization and metastases occurring in malignant tumors. No significant financial relationships to disclose.