Ton Schumacher has unravelled one of the fundamental prerequisites for cancer immunotherapy, is working in close collaboration with clinical researchers to bring immunotherapy to patients, and has set up several spin-offs to ensure that the treatments that he is devising will actually be developed. Schumacher is a member of Oncode Institute, the virtual Dutch cancer research institute.
Fundamental research
How does the immune system work? That was the question that fascinated Ton Schumacher as a young scientist. 'My original motivation was pure scientific curiosity', he says. Over the years, however, he has increasingly felt an urgent need to do something with that knowledge.
His early work, in the 1990s, was as yet unrelated to cancer. 'We were particularly looking for cells infected by a virus. At that time I just had no idea that that knowledge would be so useful. For me, then, cancer immunotherapy is a real victory of basic research.'
How does a T cell know that it should attack a cancer cell?
In 2018 two fellow pioneers of cancer immunotherapy, Jim Allison and Tasuku Honjo, were awarded a Nobel Prize. They wanted to know what the brakes on the immune system are. Schumacher's question is actually even more fundamental: how does a T cell even know that it should attack a tumour cell? What makes a T cell look at a tumour cell and think, 'that shouldn't be here'?
DNA damage
The key turned out to be DNA damage: the more DNA damage, the better the immune response. Cancer cells that have a lot of DNA damage present brand new protein fragments on their surface (neoantigens) that are absent on healthy cells. These alert the T cell. As a consequence, a dormant immune response develops in many patients, which can be amplified by immunotherapy.
Practice has proved Schumacher right. The types of cancer that have relatively high levels of DNA damage respond particularly well to immunotherapy - melanoma (sun damage) or lung cancer (damage due for example to smoking), for instance.
Measuring patients' immune responses
Schumacher and his group are developing technology to measure patients' immune responses. He has developed this technology at the Netherlands Cancer Institute van Leeuwenhoek Hospital, with Huib Ovaa. Huib died a month ago, far too young, so the prize is a homage to him too, says Schumacher.
Schumacher will use 2,5 miljoen euros to build an algorithm which can predict whether a T-cell is able to recognize cancer cells.
Clinical trials
Schumacher's habitat is the lab, but he works with the hospital oncologists on a daily basis. He has initiated a series of innovative clinical trials at the Netherlands Cancer Institute along with clinical researchers John Haanen and Christian Blank. 'There is a continuous flow of information in both directions between the lab and the hospital', he says.