Helping immunotherapy work better for children with neuroblastoma by reprogramming the tumour environment

The challenge

Neuroblastoma is a type of cancer that mostly affects children under the age of five. While some children respond well to treatment, those with high-risk neuroblastoma often face harsh treatments with serious side effects and only around half survive long-term. Gentler and more effective new treatments are urgently needed. 

One promising option is a type of immunotherapy called CAR T-cell therapy, which uses a child’s own immune cells, which have been reprogrammed in the lab to find and destroy cancer. This approach has worked well in certain blood cancers, but it has not yet been successful in solid tumours like neuroblastoma. A big reason is that the cancer creates an environment that prevents immune cells from working properly inside solid tumours.

The project

Professor James Arnold at King’s College London and University College London-based researchers Professor John Anderson and Dr Thomas Jackson want to create a smarter, more powerful type of CAR T-cell. Their treatment aims to attack the cancer, but also to make it easier for the immune system and the CAR T-cells to fight inside the tumour. 

The team will develop a new kind of CAR T-cell that will hunt down tumour cells which express high levels of a certain protein. This protein is more common on neuroblastoma cells than healthy cells, which will mean the treatment is less likely to harm healthy cells. These CAR T-cells will also carry a special signal that can help immune cells talk to each other and fight more effectively. To keep children safe, the researchers will also build in a validated and tightly controlled ‘on-switch’ that only activates the immune signal when the T cells are inside the tumour. They hope that this will reduce the risk of side effects and ensure that the T cells are saving their cancer-fighting power for when they reach the tumour. The treatment will be tested in the lab to find out how well it controls the cancer, how it changes the tumour environment, and whether this helps other immune-based treatments work better. 

The impact

If successful, this project could lead to the first clinical trial of this treatment for children with high-risk neuroblastoma. By making immunotherapy work better in these difficult-to-treat cases, the team hopes to give children a better chance of survival with fewer long-term side effects.