Immunotherapy is one of the most promising treatments for certain cancers. At UCL, several research teams are studying our immune mechanisms to find new treatments.
Every day our bodies face internal and external attack from viruses, bacteria, fungal infection, cellular reproduction failure, etc. To prevent them from spreading, making us ill and, possibly, killing us, nature provided us with a set of defence mechanisms called the immune system. It’s army of tiny soldiers, lymphocytes, fight our attackers, which they identify by the antigens present on threatening cells and that, normally, trigger an immune response.
Cancer immunotherapy origin and principle
Twenty-five years ago, Thierry Boon, a UCL professor and researcher, discovered the existence of antigens found on the surface of cancerous cells and specific to tumours. ‘These antigens can be seen as small, abnormally coloured flags’, explains Prof. Sophie Lucas, an immunologist at the UCL de Duve Institute. ‘Taking the example of cancer, while healthy cells have small white flags, the flags of cancerous cells are red, blue, green, etc. The immune system sees them as abnormal. But for reasons not entirely clear, it either doesn’t attack or can’t manage to destroy the cancerous cells. As a result, the cells proliferate and the cancer grows.’
Boosting the immune system, and helping the tiny soldiers do their job—attack and destroy cancerous cells—is the principle of cancer immunotherapy: using the patient’s own immune system to treat his or her cancer.
In recent years, several types of immunotherapy have been developed and tested around the world, more or less successfully. ‘When it works, the results can be spectacular!’ Prof. Lucas says. ‘Remissions of melanoma, lung cancer, lymphoma. Unfortunately, immunotherapy works only in 20 to 50% of cases and serious side effects are possible.’
The immune fire and its firefighters
The main risk when tinkering with the immune system is that it might turn against the patient and provoke an auto-immune disease, because when it faces an attacker, the immune system doesn’t mess around. ‘It’s designed to react explosively, brutally and intensely,’ explains Prof. Lucas. ‘Like a fire that catches suddenly. So nature provided a mechanism to temporise and interrupt it. That’s the role of regulatory T cells, or “T-regs”, which inhibit other lymphocytes when necessary. T-regs protect us against auto-immune diseases. If they didn’t exist, it’s quite simple: our immune system would turn against us and destroy us from within.’
In short, T-regs are the immune system’s firefighters. They put out the immune ‘fire’ by dampening the ardour of its lymphocyte soldiers.
Overzealous firefighters
In cancer patients, this becomes a problem: the T-reg firefighters overreact. The teams of Prof. Lucas and another UCL immunology researcher, Prof. Pierre Coulie, try to understand how T-regs work. ‘We discovered that owing to a protein on their surface called GARP, T-regs produce a hormone, the cytokine TGF-beta. To resume our metaphor, GARP is the firefighter’s fire hose and TGF-beta is the water. In the case of cancer, the T-reg firefighters amass in the tumour and flood it with water. This paralyses the immune soldiers, who then can’t do their job.’
Once they understood this mechanism, researchers from UCL and arGEN-X, a Ghent biotechnology company, created a new antibody. ‘It blocks GARP: it “turns off” the T-reg firefighters’ fire hose, preventing them from doing their job, and frees the lymphocyte soldiers to attack cancerous cells.’ Preclinical and clinical studies must still be conducted. If all goes as planned, we’ll soon have a new form of immunotherapy for treating certain cancers, without provoking auto-immune disease.
Candice Leblanc
Prof. Lucas’s research is or has been funded mainly by FNRS, WELBIO, the European Union, and the Belgian Foundation against Cancer.
A Glance at Sophie Lucas's bio
A Glance at Pierre Coulie's bio
