Blockade of the CCR8 chemokine receptor as novel cancer therapy (FWOSB24)

Over the past decades, survival rates and life expectancy of cancer patients have increased tremendously thanks to the development of efficient therapies that target cancer cell behavior. However, tumors do not only contain cancer cells, but also many normal cells that contribute to the formation of blood vessels and connective tissue, and suppress anti-tumor immunity. Hence, these normal tumor-associated cells may contribute significantly to tumor growth and dissemination, and are therefore considered as interesting novel targets for cancer therapy. We identified the chemokine receptor CCR8 as a molecule expressed on non-cancerous cells that contributes to tumor growth, as was demonstrated by a reduced tumor growth rate in CCR8-deficient mice. Reduced tumor growth is secondary to the induction of an efficient anti-tumor immunity, suggesting that CCR8 mediates the establishment of an immune suppressive tumor environment. This is important novel knowledge, since the efficacy of immune checkpoint blockers (a novel class of immunotherapeutic agents that are considered as breakthrough medicines) is hampered by a suppressive tumor environment. Therefore it makes sense to block CCR8 as a means to subvert the immune suppression in tumors. In this project, we will generate CCR8 blocking Nanobodies and small molecule antagonists and we will assess their potency as monotherapy, or in combination with immune checkpoint blockade.

Keywords:cancer therapy, biology

Disciplines:Systems biology not elsewhere classified