ARGX-115

This is the story of Professor Sophie Lucas and her research team at the de Duve Institute, located on the medical campus of the University of Leuven. Prof. Lucas and her team partnered with scientists at argenx to come up with a potential therapy.

Prof. Lucas explains the role of our immune system: “We know that the immune system in humans is mainly to defend ourselves against infections, like viral infections, bacterial infections, and parasitic infections.” 

It has been clearly demonstrated that the immune system can recognize cells as abnormal and initiate a process to eliminate them. Simplified, this is the remarkable role the immune system can play in surveillance

There are many different reasons why the immune system can lose its ability to identify or eliminate a tumor—in this scenario, the tumor cells escape surveillance by the immune system. Many labs today are trying to understand how tumor escape works, asking questions like: How and why does this happen? How can we stop it? 

Prof. Lucas explains that there are various reasons tumor escape occurs: “Either the immune cells cannot recognize tumor cells because the tumor cells have become resistant to killing, or else the immune cells have become paralyzed.” 

In order to overcome tumor escape, “We have to boost the immune system again, to start doing its work, which is to eliminate cells. This is what we call immunotherapy.” 

“Some cells in the immune system are specialized in recognizing and eliminating tumor cells. Other cells in the immune system, called Tregs or regulatory T-cells, are dampening immune responses to prevent autoimmunity or autoimmune diseases. We found that these Tregs function thanks to a molecule on their surface called GARP, which tells the Tregs to exert their inhibitory function.” 

In this way, a GARP inhibitor could have the potential to reactivate the immune system to eliminate cells. 

The GARP partnership was the first one that Prof. Lucas established with us: “My lab was already working on Tregs and GARP and we had derived our own antibody with our usual technology. Together with argenx, we thought it could be nice to develop a similar [anti-GARP] antibody to the one we already had—but using argenx’s platform. The platform is extremely well-adapted and works beautifully to produce antibodies that have therapeutic value.”

“What we have done together with argenx is develop an antibody that can block the function of GARP on the surface of Tregs. Blocking GARP helps to stop the function of Tregs, and to hopefully restore the function of the anti-tumor T-cells that are supposed to eliminate the tumor.”