Immunotherapy is a relatively new and promising way to treat cancer, which involves using the immune system to attack tumor cells in a highly targeted manner. How does an immune cell know whether a body cell is good, bad or really bad? Is a cell 'the good', 'the bad' or 'the ugly'? Stefan Nierkens PhD, group leader and specialist in immunotherapy, took the audience into the wonderful world of the immune system.
This story starts with the gatekeepers, the dendritic cells. They control cells and clean them up if necessary. They also crack the code laid down in bad cells and signal the so-called B and T cells to take action. 'These 'nerds' of the immune system are not that fast, but they are very specific. And that is precisely their strength; they only attack the bad cells and leave the good ones alone,' says Nierkens. Tumor cells, however, have the characteristic of deceiving this system, their growth continues and treatment is required.
Antibody as a driver of the attack
Miranda Dierselhuis MD, PhD, is a pediatric oncologist specialized in the treatment of solid tumors and neuroblastoma in particular. Part of the treatments she gives is immunotherapy with the antibody anti-GD-2. 'Antibodies are made by B cells during a normal immune response. The antibodies for this immunotherapy are made in a laboratory,' Dierselhuis says.
The discovery of a common denominator on neuroblastoma tumor cells, protein GD2, made it possible to develop a therapy, antibody GD-2. 'By binding the antibody GD-2 to the tumor cells, the non-specific part of the immune system initially comes into action. The cell death that then occurs allows T-cells to crack the code that has been captured in bad cells. This triggers the attack by T cells and 'memory' T cells are produced. These remain in the body as a 'memory' and spring into action when the tumor cells return.' Anti-GD2 immunotherapy thus works in two ways: by specifically attacking the cancer cells, and by making the immune system more alert if the cancer returns. 'This has reduced the chance of cancer returning after a child has been cured by 15 to 20%. We are also doing a lot of research to make anti-GD2 immunotherapy work even better and to see whether we can give it earlier in the treatment.'
One and one is three
One very promising form of immunotherapy is treatment with modified T cells, also known as CAR T. We combine the properties of B- and T-cells and thus attack the tumor cells in a very targeted way and activate large amounts of T-cells. CAR T treatment is not only effective to cure but also to prevent recurrence,' says Calkoen, pediatric oncologist specialized in hemato-oncology and CAR T cell treatment.
'The patient's own T-cells are used for this treatment. Outside the body the cells are multiplied and modified. Then we give the cells back via an infusion. Now the cells have to go to America for this, but soon we will be able to do this ourselves in Utrecht.'
At the moment, treatment with CAR T cells is only possible for children with acute lymphoblastic leukemia (ALL) or lymphoma. 'In addition to research into a broader application, we also want to find out more about how we can keep CAR T cells in the body for longer and what the best time for the infusion is. We are also looking at whether we can predict the likelihood of success. In short, we have successfully made our first steps in this field, but are looking forward to what else is possible.'
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