Creating a new immunotherapy approach to fight aggressive medulloblastoma

Medulloblastoma is one of the most common types of childhood brain tumour, which has four subtypes. Group 3 is one of the highest-risk subtypes, and only one patient out of twenty will survive this type of medulloblastoma. They are also much more likely to have their cancer return after treatment, at which point it cannot be cured. Whilst there have been fantastic improvements for many medulloblastoma patients, the physical and mental cost to survivors is high and high-risk tumours are still very difficult to treat. This shows that children with medulloblastoma desperately need new targeted treatments that cause less damage to their growing brains.

CAR-T therapy has shown lots of promise for some types of cancer, like leukaemia. This treatment trains a patient’s own immune cells to hunt down and kill cancer cells, based on proteins on the cancer cell surfaces, called antigens. However, medulloblastoma cells can have very varied antigens, meaning that the CAR-T cells cannot find the cancer, and these trained cells do not always survive for long inside the body.

To address this, Dr Laura Donovan from the Institute of Child Health has developed a ‘dual’ CAR-T cell that can recognise two different antigens. By targeting two antigens rather than just the one, her team’s treatment will overcome the issues of medulloblastoma cells showing different antigens and also improve the chance of the CAR-T cells locking on to the cancer cells.

In this project, Dr Laura Donovan’s team will be working out the best way to use their new treatment. They will be testing different versions of dual CAR-T cells and investigating their effect on medulloblastoma cells. By finding out exactly how the CAR-T cells work, and which are the most effective versions, the researchers hope to generate enough evidence to get their treatment into clinical trials.