Recombinant human VEGF165b protein is an effective anti-cancer agent in mice

Abstract Tumour growth is dependent on angiogenesis, the key mediator of which is vascular endothelial growth factor-A (VEGF-A). VEGF-A exists as two families of alternatively spliced isoforms – pro-angiogenic VEGF xxx generated by proximal, and anti-angiogenic VEGF xxx b by distal splicing of exon 8. VEGF 165 b inhibits angiogenesis and is downregulated in tumours. Here, we show for the first time that administration of recombinant human VEGF 165 b inhibits colon carcinoma tumour growth and tumour vessel density in nude mice, with a terminal plasma half-life of 6.2 h and directly inhibited angiogenic parameters (endothelial sprouting, orientation and structure formation) in vitro . Intravenous injection of 125 I-VEGF 165 b demonstrated significant tumour uptake lasting at least 24 h. No adverse effects on liver function or haemodynamics were observed. These results indicate that injected VEGF 165 b was taken up into the tumour as an effective anti-angiogenic cancer therapy, and provide proof of principle for the development of this anti-angiogenic growth factor splice isoform as a novel cancer therapy.