Projects we fund

Overview

Treating children with tumours that resist chemotherapy, especially when the tumours have spread to other parts of the body (metastasised), is one of our greatest challenges. Professor John and his team want to develop new immunotherapy approaches using an approach called ‘adoptive immunotherapy’. The child’s own blood cells are genetically modified in the laboratory to recognise a particular target (called an antigen) and then injected back into them. When the cells, called ‘chimeric antigen receptors’ (or CARs), encounter an antigen it triggers an immune response. CAR trials have revolutionised how we treat chemotherapy-resistant leukaemia, especially acute lymphoid leukaemias. We’ve seen unprecedented and lasting clinical remissions in many people who haven’t responded to chemotherapy following disease relapse. Now we need to know whether the same can be achieved with solid tumours.

What difference will this project make?

The team has already carried out pioneering research on CAR technology in neuroblastoma, and in 2016 opened a clinical trial based at GOSH, using an antigen called GD2 as its target. Crucially, there is a lot of GD2 on the surface of neuroblastoma cells, but little or none on most normal tissue. Genetically modified blood cells are triggered by GD2, and mount an immune response against the cancer cells. They are now looking at childhood sarcomas, solid tumours that can occur in bone or soft tissue, including Ewing sarcoma, osteosarcoma and rhabdomyosarcoma. These cancers are very hard to treat if they relapse or metastasise. GD2 has been reported in these sarcomas so the team wants to apply CAR technology. In this project, they’ll analyse tumour tissue from children with sarcomas to understand which groups are most likely to benefit from this type of immunotherapy. Then they’ll compare different types of CAR and immune cells for their ability to kill sarcoma cells in the laboratory. This work should result in the development of a new clinical trial, with the realistic potential for effective treatment for children where chemotherapy has failed. An immunotherapy approach should also have minimal toxicity – with reduced risk of side-effects. This work will also benefit the immunotherapy field generally, giving new insights into the treatment of childhood cancer. In particular, the team is exploring the use of a novel cell type for CAR treatments which could have a more powerful effect than the cells conventionally used.