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Vascular endothelial growth factor (VEGF) is an important signaling proteinand a predominant mediator of angiogenesis in tumor growth and metastasis. Therefore,antagonism of the VEGF pathway results in inhibition of abnormal angiogenesis,then suppression of tumor growth and metastasis. VEGF-Trap, a high-affinity solubledecoy receptor, is currently in phase II clinical trails, and has demonstratedmore efficacy in different types of solid tumors by intravenous injection everytwo weeks. In our study, we used recombinant AAV2 as a delivery vehicle to achievelong-lasting expression of VEGF Trap protein in a mouse model for the first time.We report that AAV2-VEGF-Trap can be safely administered and sustained expressionin vivo via a single intravenously administration, simultaneously suppressingprimary tumor growth and preventing the pulmonary metastases of 4T1 tumors. Decreasedmicrovessel density and increased tumor cell apoptosis were observed in the treatmentgroup. AAV2-VEGF-Trap can obviously decrease not only the concentration of VEGFin sera, but also the concentration of other angiogenic factors, such as aFGF,bFGF, angiopoietin-1 and others. These studies suggest that AAV-mediated long-termexpression of VEGF-Trap is a useful and safe tool to block tumor progression andinhibit spontaneous pulmonary metastases.

oncology reports

AAV2-mediated gene transfer of VEGF-Trap with potent suppression of primary breast tumor growth and spontaneous pulmonary metastases by long-term expression