Immune Interest of a rhenium-selenium compound

What is it about?

This paper is about a therapeutic application of an organo-metallic compound of rhenium, called rhenium(I)-diselenoether, which is a combination of one atom of rhenium (Re) and two atoms of selenium (Se). This water soluble drug has already demonstrated its selective inhibitory effects on malignant cells in culture and its antitumor activity on experimental models of triple-negative beast cancers. It has anti-oxidant properties. An immunotherapeutic application is now designed. Proteolytic enzymes, cathepsins cysteine proteases are increased in cancer cells and in immune cells. They are involved both in cancer development and in immuno-resistance of the cancer cells. By decreasing the production of cysteine proteases B and S, rhenium(I)-diselenoether is able to modulate the phenotype of macrophages, innate immune cells, when these macrophages are stimulated by inflammatory cytokines. It was thus demonstrated that the drug induced a dramatic dose-dependent increase in classically activated M1 macrophage phenotype and significantly decreased the alternatively activated M2 macrophage expression in stimulated macrophages and had no effect in non-stimulated macrophages. The classically M1 macrophage activation is crucial for killing cancer cells, while M2 macrophages are known to exert an immune suppressive phenotype, favoring tumor resistance. Increasing M1 and decreasing M2 phenotypes will then induce a favorable immune effect in the fight of the cancer immuno-resistance.

Featured Image

Why is it important?

It is a completely new immunotherapeutic approach in cancer, with different targets than the immune check-point inhibitors which are widely used in different types of cancers. The targets are the cysteine proteases. It has been demonstrated that the Re atom could bind with the thiol (SH) groups of cysteine and could therefore inhibit the activity of the cysteine proteases.

Perspectives