Some childhood cancers don’t respond well to chemotherapy, but there is hope in the form of immunotherapy. Doctors have already achieved success using immunotherapy techniques to treat children with leukaemia and neuroblastoma. Now Professor John and his team aim to extend these techniques to treating childhood sarcomas.
For childhood cancers that don’t respond well to chemotherapy, immunotherapy offers new hope. Children with leukaemia and neuroblastoma have already been successfully treated, and this project by Children with Cancer UK aims to extend immunotherapy to treating childhood sarcomas.
Developing GD2-targeted cellular immunotherapy for childhood sarcomas
Professor John Anderson
Institute of Child Health, University College London
London WC1N 1EH
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.
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.
John Anderson is Professor of Experimental Paediatric Oncology at UCL Institute of Child Health and Honorary Consultant Paediatric Oncologist at Great Ormond Street Hospital. He is a leading authority in developing and applying immunotherapy techniques for childhood cancers. His group works closely with Dr Martin Pule of the UCL Cancer Institute, who has pioneered much of the CAR technology available for this project.
The team is uniquely placed in the UK to carry out this work, with facilities for the manufacture of cell products for gene therapy approaches, and the infrastructure at Great Ormond Street Hospital for delivering gene therapy trials in children.
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