Children with high-risk neuroblastoma have poor chances of surviving their disease. Five years after diagnosis, fewer than half of children are still alive, despite a heavy treatment plan that combines different types of therapy. Immunotherapy is a promising new form of cancer treatment that uses the body’s own immune cells to attack and destroy cancer cells in a targeted manner.
Not effective enough
For several years, children with high-risk neuroblastoma have been treated with the immunotherapy drug dinutuximab. Although this drug has led to some improvement in survival, underwriting the promise of immunotherapy, the therapy is not yet effective enough to lead to a cure in all children. One in three of them will see their disease come back after treatment. The reason for this is that neuroblastoma tumors can shield themselves from immunotherapy in multiple ways. Neuroblastoma tumors send signals that block the child's immune cells. As a result, the immune cells are no longer able to clear the tumor or prevent the tumor from coming back.
Multiple approaches to better treatment
Dr. Judith Wienke, postdoctoral researcher in the Molenaar group at the Princess Máxima Center: ‘In this unique collaborative project, we are working on multiple approaches to new, better treatments for children with neuroblastoma. We are simultaneously looking at ways to release the brakes on the immune system and at new targets for immunotherapy in neuroblastoma. With new, cutting-edge techniques, we can take important steps in the development of immunotherapy for this hard-to-treat form of childhood cancer.’
‘Flags’
By imaging each individual cell in neuroblastoma tumors, the researchers aim to find out why the immune cells no longer work properly. The researchers then hope to restore this. Another problem is that it’s difficult for the immune cells to recognize neuroblastoma tumors because there are few recognition points. To do this, the scientists will map out new, small recognition points – a kind of 'flags' – on the tumor cells using a new technique. The researchers plan to use these flags to train the child's immune cells outside the body to recognize neuroblastoma cells, and to activate the immune cells so that they are less sensitive to the tumor’s signals stopping them.
The most promising therapies from this research will first be investigated in a future clinical study to test the safety and effectiveness for children with recurrent or difficult to treat neuroblastoma.
The research groups in the Princess Máxima Center involved in this collaboration are the Molenaar (dr. Judith Wienke and prof. dr. Jan Molenaar), Nierkens (dr. Stefan Nierkens and dr. Annelisa Cornel) and Van Heesch (dr. Sebastiaan van Heesch) groups, in close collaboration with pediatric oncologist dr. Miranda Dierselhuis and prof. dr. Max van Noesel, clinical director of the Solid Tumor department at the Princess Máxima Center.