CD Laboratory for Immune therapy-mediated cancer rejection via NR2F6 blockade

Great hopes are currently associated with cancer immunotherapy, but it is still in its infancy. This CD Laboratory is now breaking completely new ground to enable the body to defend itself against the tumour.

The immune system is equipped to recognise and eliminate cancer cells. However, there are inhibitory receptors and ligands that keep the immune system in check, the so-called immune checkpoints. In healthy people, this is done to prevent damage to the surrounding tissue or even autoimmune reactions in the course of an immune response. Cancer cells, however, can hijack these immune checkpoints and their mechanisms and thus circumvent their destruction by the immune system. The latest cancer therapies now target precisely these immune checkpoints. They enable the body to really dissolve the cancer using the body's own defence cells, so-called T cells.

This CD Laboratory is dedicated to the study of the immune checkpoint NR2F6. In contrast to other approaches in the field of immune checkpoints, where expensive synthetic antibodies bind to the immune checkpoints PD-1 and CTLA-4 on the cell surface, NR2F6 is located inside the cell, more precisely in the cell nucleus, and can be pharmacologically inhibited with small molecule drugs. Such novel drugs therefore offer a promising opportunity, affordable by health insurance companies, to treat cancer with a good quality of life for those affected and over a long period of time.

The research work is divided into two areas. The first research area aims to expand basic knowledge about the importance and position of NR2F6. There are initial indications that NR2F6 could be used as a biomarker for tumour detection, as NR2F6 is strongly upregulated in some patients. However, NR2F6 needs to be further studied and validated for use as a tumour marker. There are also indications that the inhibition of NR2F6 could increase the effectiveness of antibodies to inhibit PD-1 and CTLA-4 and thus lead to savings in these expensive drugs. Finally, two methods of inhibiting NR2F6 are compared, namely pharmacological inhibition using small molecules and inhibition based on RNA interference (siRNA; small interfering ribonucleic acid). siRNA binds to the NR2F6 mRNA and thus inhibits the expression of this gene.

The second research area is concerned with the discovery of drugs that can inhibit NR2F6. Here, it must first be understood which classes of molecules are structurally suitable for inhibition and exactly how this inhibition takes place. Based on this knowledge, new molecules can be specifically designed and particularly effective molecules can be identified (hit-to-lead development). Furthermore, natural ligands will be identified that bind NR2F6 in the context of its natural positions and regulate them. The natural ligand of NR2F6 is not yet known. Finally, the molecules that have proven to be the most effective in previous research steps (lead compounds) will be tested in mouse models.

This CD Laboratory is searching for a completely new type of cancer immunological agent that could potentially bring humanity one step closer to curing at least some types of cancer."