Creating a new combination treatment for children's brain tumours

Brain tumours are the most common type of solid tumour in children, but are sadly very difficult to cure. Treatments are very intensive, and so children who do survive are often left with serious long term side effects. In recent years, immunotherapy has become a treatment option, which can be a lot kinder.

CAR-T cell therapy is one of the main types of immunotherapy used to treat cancer. It has been very successful for leukaemia, which is a type of blood cancer, but hasn’t worked as well for solid tumours. Doctors take a patients own immune cells, called T-cells, and train them to hunt down cancer. A key part of this is deciding how the T-cells will recognise cancer cells.  CAR-T cells have a tiny protein on their surface, called CAR, which doctors can edit to recognise different tiny proteins on cancer cell surfaces. When the CAR-T cell encounters a cancer cell with the specific protein it is edited to recognise, it will activate processes that kill the cancer cell.

Professor John Anderson, with his team at University College London Great Ormond Street Institute, wants to create a new type of CAR-T therapy that will work for childhood brain tumours. The researchers have already selected the cancer protein they want to target, called B7H3, and have a plan to make their immunotherapy more successful for solid tumours. They have developed a way to turn the CAR-T cells on and off, using an existing group of drugs called IMiDs. This will allow the CAR-T cells to be switched off for rest and recovery – researchers think that one of the reasons CAR-T therapy isn’t as effective in solid tumours is because they become ‘exhausted’.

This project will test the combination of IMiDs with the new CAR-T cells in a number of childhood brain tumour lab models. If successful, Professor Anderson hopes to progress this treatment into clinical trials to create a safer and more effective treatment for children with brain tumours.