Harnessing the immune system to treat Ewing sarcoma in the lungs

The challenge

When bone tumours such as Ewing sarcoma and osteosarcoma spread to the lungs (known as metastatic cancer), 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. Some types of immunotherapy involve collecting immune cells from patients and genetically engineering them so that they are able to recognise and kill cancer cells. The immune cells are then returned to the patient. Whilst effective, this process is both costly and time-consuming.

An exciting alternative is an ‘off the shelf’ version of immunotherapy, which uses immune cells of healthy donors. However, using standard 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.

The project

Researchers at the UCL Great Ormond Street Institute of Child Health, led by Dr Jonathan Fisher, have expertise in a type of immune cell called '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.

To optimise treatment in primary bone cancers, the γδT cells can be combined with drugs which direct them towards bone (called ‘bone sensitising agents’). However, in metastatic Ewing sarcoma, relapses occur outside the bone, most commonly in the lungs. This project will investigate the use of sensitising agents that will enable targeting of the γδT cells to the lungs rather than to bones. 

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.

The impact

Metastatic Ewing sarcoma is a major challenge and affects both survival and quality of life for patients. This research aims to address this problem, taking steps towards 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.