Fine-tuning a new CAR T cell and drug combination for testing in solid childhood cancers

The challenge

CAR T cell therapy is an exciting step forward in childhood cancer treatment. It works by taking a child’s own immune cells and training them to find and attack cancer cells. This has been very effective for some types of childhood blood cancer, such as leukaemia, but hasn’t worked as well for children with solid tumours. It is harder for CAR T cells to reach the cancer cells inside the tumour, and once there, the tumour environment often overwhelms the immune cells. As a result, the CAR T cells become exhausted and stop working properly before they can finish fighting the cancer.  Finding ways to help CAR T cells survive and stay active for longer is one of the biggest challenges in the field.

The project

Professor John Anderson’s team has developed a new type of CAR T cell designed specifically for childhood solid tumours. These CAR T cells target a molecule called B7H3, which is found on the surface of cancer cells in most high-risk childhood tumours like sarcomas and neuroblastomas. 

Called ‘drug switchable CAR T cells’, Prof Anderson’s treatment can be controlled by a specific anti-cancer drug. This allows doctors to ‘switch off’ the CAR T cells with the drug, forcing them to rest and recover. At the same time, the drug makes the tumour less able to protect itself from the immune system. When the drug is stopped, the CAR T cells are switched back on and can continue effectively fighting cancer. 

Previous work funded by The Little Princess Trust helped the team identify the best pattern of ‘on’ and ‘off’ treatment to support CAR T cell recovery. In this project, Professor Anderson and his team will now compare two slightly different versions of these switchable CAR T cells in the laboratory to identify the strongest and safest option to take forward. This work directly supports an upcoming early phase clinical trial in children whose cancers have returned or have not responded to standard treatments.

The impact

Children with high risk solid tumours urgently need kinder, more effective treatment options. Recent clinical studies have shown that CAR T therapy can lead to lasting benefits if the treatment cells are able to remain active in the body for long enough. The results of this project will directly shape upcoming clinical trials and bring innovative treatments closer to children who currently have very few options.