Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Juliet Gray, University of Southampton
Award: £198,167.49
Awarded July 2023
Neuroblastoma is one of the most common and most aggressive childhood cancers. Most children with this tumour have ‘high-risk’ neuroblastoma, which is very difficult to treat with current treatments like chemotherapy, surgery or radiotherapy.
Recently, immunotherapy has been combined with standard treatments to improve survival, but less than half of the children with high-risk neuroblastoma are cured. The immunotherapy sometimes uses antibodies, which are proteins made by the immune system to hunt down and fight harmful things in the body like viruses and bacteria, to find and kill cancer cells. For neuroblastoma, antibodies are made in the lab to target a molecule found on neuroblastoma cells, called GD2.
However, these man-made antibodies also have significant side effects. One of the main side effects is pain, because the GD2 molecule which the treatment targets is also found on nerve cells. Children who survive neuroblastoma will often also have long-term side effects of treatment.
Dr Juliet Gray at the University of Southampton wants to develop a new type of immunotherapy that is safer and more effective. In this project, she plans to create this treatment by modifying the current anti-GD2 antibody.
- Dr Gray’s team will combine part of the anti-GD2 antibody with part of an antibody that binds to a different molecule found on neuroblastoma cells, called B7-H3. The B7-H3 molecule is not found on normal nerve cells, and so this will make the antibody more specific to neuroblastoma cells. She hopes that this treatment would cause less pain, meaning children would require less morphine and spend less time in hospital.
- The researchers will also add another piece to the antibody so that it also targets a third molecule called CD3. This molecule is found on cells of the immune system, so this addition could help attract immune cells to the tumour, which would kill the cancer cells. This is a different way of killing tumour cells to current anti-GD2 antibodies, and has been shown to be very effective in leukaemia.
Dr Gray plans to make multiple versions of these antibodies to find out which are most effective at attracting immune cells and killing tumours in the lab. The most promising treatment will be tested further to see how it effects tumour growth and whether there are significant side effects. Dr Gray and her team hope that their three-pronged approach to immunotherapy will be safer and more effective, leading to fewer side effects and more children being cured.