When bone tumours such as Ewing sarcoma and osteosarcoma spread to the lungs, they are much harder to treat. This remains a major challenge despite intensive chemotherapy and radiotherapy, both of which cause major side effects. Furthermore, cancer cells can become resistant to these harsh treatments, leaving even fewer options. Immunotherapy, using the power of the immune system to attack the cancer, is emerging as a strategy to address this challenge.
Immune cells are cells in the blood which fight infection. Some types of immunotherapy involve collecting immune cells from patients and genetically engineering them so that they are able recognise and kill cancer cells. The immune cells are then returned to the patient. Whilst effective, this process is both costly and time consuming, and the patient’s cancer may progress in the meantime.
An exciting alternative is an ‘off the shelf’ version of immunotherapy, which uses immune cells of healthy donors. Normally, using donor cells carries the risk of ‘graft versus host disease’, where the donated immune cells recognise the patient’s body as ‘foreign’ and mount an attack against it.
However, researchers led by Dr Jonathan Fisher, based at the UCL Great Ormond Street Institute of Child Health, have expertise in a particular type of immune cell known as gamma-delta T cells (γδT). These cells do not cause graft vs host disease and therefore represent a safe and exciting alternative. The team have already demonstrated that genetically engineered γδT cells can effectively kill cancer cells in laboratory models of Ewing sarcoma when combined with cancer-targeting proteins (antibodies). They have also developed a technology in which γδT cells are engineered to secrete antibodies capable of treating laboratory models of osteosarcoma.
What are the aims of this research project?
To optimise treatment in primary bone cancers, the γδT cells can be combined with drugs which direct them towards bone (so called ‘bone sensitising agents’). However, in Ewing sarcoma, relapses occur outside the bone, most commonly in the lungs.
The aim of this current project is therefore to investigate the use of alternative sensitising agents, to enable targeting of the γδT cells to places other than the bones, specifically the lungs.
Dr Fisher and team will also set out to understand how the effectiveness of this potential new treatment approach may be influenced by other cells normally present in the lungs.
How could this project improve treatment options for Ewing sarcoma patients?
The treatment of Ewing sarcoma which has spread elsewhere in the body represents a major challenge which, unless overcome, comprises both survival and quality of life for patients. This research looks to address this major unmet need and take steps towards developing a more targeted, more effective treatment.
Dr Fisher and team will build on the successes of their previous research, which has already demonstrated the potential of their genetically engineered γδT cells to target bone cancer cells and reduce tumour growth. If successful, these next stages of research could help to translate these exciting pre-clinical findings from the laboratory to the clinic.
This is one of four pioneering projects funded as part of a groundbreaking £800,000 joint investment into Ewing sarcoma research, made possible thanks to a collaboration between the Bone Cancer Research Trust, CCLG - The Children and Young People's Cancer Association, the Ewing's Sarcoma Research Trust and Great Ormond Street Hospital Charity.
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