Tumour angiogenic vessels are considered an attractive target for the development of therapeutics. One of the prime targets is VEGF, the major growth factor for blood vessels. However, the anti-VEGF therapies have shown limited efficacy resulting in only a transient effect of tumour growth but also resulting in an increase in tissue hypoxia that ultimately promotes tumour growth and limits radio- and immune therapy.

Tumour angiogenic blood vessels are characterised by both structural and functional changes. Thus, they are tortuous, lack adequate pericyte coverage and the matrix shows changes in density and composition. These changes result in increased permeability, reduced perfusion and the tissue environment is hypoxic. The concept of vessel normalisation has been proposed as an alternative to ablation of tumour angiogenic vessels. In normalisation, the vessels are converted back to a structurally more normal architecture and function, with the potential to enhance radio- and chemotherapy.

We have developed a first-in-class normalisation agent (CD5-2) that with a single intravenous injection significantly enhances in mice tumour vessel perfusion and pericyte coverage, decreases vascular leak and tissue hypoxia and inhibits tumour growth. CD5-2 increases the expression of the major structural endothelial cell specific junctional adhesion molecule VE-cadherin and also has a highly significant downstream effect on at pathways involved in vessel stabilisation. CD5-2 has a number of unique properties, in being soluble in saline, having long-lasting tissue distribution, effects from a single intravenous dose and targeting an endothelial-specific gene and increasing the expression of its target.

CD5-2 is a proprietary single stranded modified oligonucleotide. The profound effects of CD5-2 are being currently examined in metastatic, cytotoxic and radiotherapy models. In an age where ‘personalised’ therapy of cancers is of great interest drugs that have potential utility across all solid cancers, and are thus ‘non-personalised’ offer a cost-effective advance.