Professor John Anderson, UCL Institute of Child Health, London
Immunotherapy is emerging as an important new line of defence against childhood cancers that do not respond to chemotherapy. Success has already been achieved in the treatment of children with leukaemia and neuroblastoma using immunotherapy techniques. Professor Anderson and colleagues now aim to extend these techniques to the treatment of childhood sarcomas.
Amount of grant: £181,213 | Date of award: May 2015
One of the greatest challenges facing paediatric oncologists is the management of children with tumours that are resistant to chemotherapy, especially when the tumours have spread to other parts of the body (metastasised).
Professor Anderson and colleagues are focused on the development of new immunotherapy approaches for this group of patients.
They are using an approach called "adoptive immunotherapy" whereby a patient’s own blood cells are genetically modified in the laboratory to recognise a particular target (called an antigen) and then injected back into the patient. The genetically modified cells, known as "chimeric antigen receptors" ("CARs"), are activated when they encounter their target, and an immune response is mounted.
CAR trials have revolutionised thinking about the treatment of chemotherapy-resistant leukaemia, especially acute lymphoid leukaemias. Unprecedented and lasting clinical remissions have been seen in high proportions of patients that have failed to respond to chemotherapy following disease relapse. Within the CAR field, one of the key questions is whether similar responses can be achieved in patients with solid tumours.
Professor Anderson and colleagues have carried out pioneering research on CAR technology in neuroblastoma and in 2016 are opening a clinical trial based at Great Ormond Street Hospital. This technology uses an antigen called GD2, present on the surface of tumour cells, as its target. Crucially, GD2 is expressed heavily on the neuroblastoma cells, but with little or no expression on most normal tissue. The patient’s genetically modified blood cells are activated when they encounter GD2 and mount an immune response against the cancer cells.
The team is now turning their attention to childhood sarcomas, solid tumours that can occur in bone or soft tissue, including Ewing sarcoma, osteosarcoma and rhabdomyosarcoma. These cancers have a dismal prognosis if they relapse or metastasise.
GD2 has been reported to be expressed in these sarcomas and the team is now looking to apply CAR technology for the benefit of this group of patients. In this project they will analyse tumour tissue from children with sarcomas to define which patient groups are most likely to benefit from this type of immunotherapy. They will then compare different types of CAR and different types of immune cells for their ability to kill sarcoma cells in the laboratory.
About the research team
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 the development and application of immunotherapy techniques for childhood cancers. His group works in close collaboration with Dr Martin Pule, of the UCL Cancer Institute, who has pioneered much of the CAR technology available for the current work.
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.
What difference will this project make?
I think the potential for success using a GD2 CAR in sarcoma is very exciting.
External reviewerThe team expects that this work will result in the development of a new clinical trial. Such a trial will increase options for young sarcoma patients at relapse, with the realistic prospect of effective treatment, where chemotherapy has failed. Further, this approach should have minimal toxicity.
This work will also benefit the immunotherapy field generally, giving new insights into the immunotherapy 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.
Read more: Osteosarcoma | Ewing sarcoma | Rhabdomyosarcoma | Patient story: Krystal