Activating a protein to make immunotherapy more effective for neuroblastoma

The challenge

High-risk neuroblastoma is one of the most challenging childhood cancers to treat. Even with intensive treatments, like chemotherapy and radiotherapy, some cancers survive and can grow back later. These intensive treatments can also damage healthy cells, so survivors are often left with serious long term side effects. 
Immunotherapy is a newer treatment that can target cancer cells more accurately and has improved survival in high-risk neuroblastoma. For many children, however, their cancer doesn’t respond. One of the reasons for this is because some neuroblastoma tumours are able to suppress the immune system. This means that the immune cells, like T cells, that are supposed to fight cancer are either deactivated or not allowed into the tumour. Immunotherapies can use a range of different immune cells and pathways, but these all rely on the immune cells being within the tumour.
 

The project

Professor Aymen Al-Shamkhani and his team at the University of Southampton want to find a way to strengthen the immune system inside neuroblastoma tumours. They hope that increasing the number of T cells inside the tumours could make one type of immunotherapy more effective, helping more children.
They hope to do this by activating a protein that is found on the surface of most cells, including neuroblastoma cells - the lymphotoxin-β receptor. Their early results suggest that activating this protein can increase the number of T cells entering neuroblastoma tumours. In this project, the researchers will further investigate this. If the researchers are able to recruit more T cells into the tumour, they will test T cell immunotherapies. They hope to see the immunotherapies activating the newly recruited T cells, making them fight the cancer.
 

The impact

Prof Al-Shamkhani hopes that this work will address neuroblastoma’s biggest barrier to immunotherapy. If the team can demonstrate a way to recruit T-cells and redirect them to kill cancer cells, it could lead to an effective new treatment combination. Ultimately, this research has the potential to deliver safer, more effective immunotherapies for children with neuroblastoma. The findings could also help researchers develop similar treatments for other cancers that currently respond poorly to immunotherapy.