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

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 VEGFxxx generated by proximal, and anti-angiogenic VEGFxxxb by distal splicing of exon 8. VEGF165b inhibits angiogenesis and is downregulated in tumours. Here, we show for the first time that administration of recombinant human VEGF165b 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 125I-VEGF165b demonstrated significant tumour uptake lasting at least 24 h. No adverse effects on liver function or haemodynamics were observed. These results indicate that injected VEGF165b 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.