This research project, which commenced in February 2017, is investigating the feasibility of using cells created by the body’s own immune system, called ‘Tumour Infiltrating Lymphocytes’ (TILs), to shrink or destroy brain tumours in children. TIL therapy is already being investigated in other cancer types but this research project focuses particularly on TILs found in types of childhood brain tumours that have a poor prognosis, such as those that don’t respond well to conventional treatments upon relapse.
Below is a project update from lead Friends of Rosie-funded researcher, Dr Gray Kueberuwa.
Within tumours there is a constant battle. The immune system attempts to destroy tumours, while tumours attempt to adapt and evolve to survive this attack. In patients that develop tumours the immune system is losing the battle. Immune cells are often suppressed or “switched off” by tumour cells.
Tumour infiltrating lymphocyte (TIL) therapy consists of extracting immune cells from surgically removed tumours and growing them in the lab. This not only allows immune cells to be “switched back on”, but increases their total number. When these cells are given back to patients, these cells can tip the battle in favour of the immune system and lead to tumour remissions.
TIL therapy is an experimental therapy that has shown great activity in treating patients with metastatic melanoma. We wish to see whether there is the potential for TIL therapy to be used in childhood brain cancers.
Patient who received TIL therapy for melanoma with extracranial metastases. A) An intracranial tumour growth was observed after infusion with TILs. B) On a pre-radiotherapy scan it was observed the tumour had shrunk, therefore radiotherapy was not given. C) 1 year on extracranial and intracranial tumours resolved, two years on, the patient is still in complete remission.
Tumour sample sizes and starting numbers of immune cells is lower in brain tumours than in many other tumour types, so part of this project has been adapting existing methods of growing immune cells to deal with small numbers of cells. Small numbers of cells also means we have less material on which to run tests when we receive tumour samples. It has, therefore, been necessary to adapt our analysis techniques to utilise the minimum amount of starting material, whilst still gaining robust results. So far this has been successful and we have been able to scale down the amount of material required for analysis by 10 fold.
So far we have seen encouraging results growing TILs. From one glioma sample, we observed a 1,300 fold expansion of TILs over a period of 2 weeks. We are hopeful that these results can be replicated in other types of paediatric brain cancers.
Crucially we are awaiting data on the health and the anti-tumour capacity of these cells after growth. This will be vital in determining the potential of this approach in this setting.
A grant extension review of this project will be undertaken by our Scientific Advisory Board over the coming weeks and recommendations for further project funding will be presented to the Friends of Rosie Board of Trustees.
Project 2 – treatment and improved detection of rare bone cancer in children
This project, which commenced in July 2017, is researching the treatment and improved detection of osteosarcoma – a rare type of bone cancer that most commonly affects children and young people. There is an urgent requirement to develop novel therapies that target metastatic osteosarcoma. In addition, better detection is pivotal to improving outcomes for children and young people with this form of cancer. If successful, the data obtained during this research could help to greatly improve the detection and treatment of patients with osteosarcoma in the future.
Below is a project update from lead Friends of Rosie-funded researcher, Dr. Katherine Finegan at The University of Manchester.
Osteosarcoma is a rare type of bone cancer that usually develops in growing bones. It’s therefore most common in children and adolescents. Surgery and chemotherapy are effective treatments for those patients whose cancer hasn’t yet spread. However, if the osteosarcoma spreads to other parts of the body, called metastasising, fewer than 30% of patients survive five years after diagnosis, a survival rate that has remained virtually unaltered over the last 30 years.
Through this project we are researching the role of a protein called, ERK5, which is believed to advance the spread of tumours. The project will aim to validate the use of ERK5 inhibitors in the treatment of the metastatic spread of osteosarcoma, whilst simultaneously developing novel molecular-imaging based methods to detect the progression of the disease.
The research team (pictured left) have also been developing some novel inhibitors (as part of another project), which we have discovered affect the growth and spread of osteosarcoma cells. The remaining 9 months of this project will involve further imaging experiments on our osteosarcoma models and targeting of a pathway that we think will prevent the spread of osteosarcoma in our models and as a result would become the basis of a future treatment for osteosarcoma patients.
The research team for this project includes Dr. Katherine Finegan, Heather Eyre (research technician), and Jason Chu (PhD student). An interim report for this project will be submitted to and evaluated by the Friends of Rosie Scientific Advisory Board in January 2018.