An Imperial team engineering new techniques in cancer immunotherapy has been awarded £1.5m over five years.
The funding, from The Brain Tumour Charity, will go towards finding a new treatment for recurring glioblastoma.
Glioblastoma is one of the most difficult brain cancers to treat, with an average survival of 12-15 months after diagnosis.
The 'Quest for Cures' grant has been awarded to Dr Jun Ishihara, a lecturer in the Department of Bioengineering at Imperial College London.
"We can explore this new treatment option, which we hope will help brain tumour patients live longer." Dr Jun Ishihara
He leads a project team engineering a new immunotherapy – a type of treatment that stimulates the body's own immune system to fight cancer to target glioblastoma.
The team is focussing on a protein called interleukin 12 (IL-12) which has demonstrated anti-tumour activity against glioblastoma cells and has long been studied as a possible immunotherapy treatment for cancer.
Dr Ishihara's team has adapted IL-12 by adding a collagen-binding site. This delivers the treatment directly to the tumour, as collagen is an abundant energy source for rapidly multiplying cells. The researchers are also using novel nanotechnology to ensure their treatment can cross the blood-brain-barrier.
Dr Ishihara said: "A glioblastoma diagnosis is devastating and there are currently limited treatment options for those affected, especially when the tumour recurs after initial treatment.
"With this funding from The Brain Tumour Charity we can explore this new treatment option which we hope will help brain tumour patients live longer."
Early trials show promise
Studies in mice using this drug have increased survival by 260 per cent and prevented recurrence and spread of the disease.
The next phase of the project involves testing the modified IL-12 treatment on different glioblastoma cells in the laboratory. These cells, each with different genetic backgrounds, will help researchers determine which cells are likely to respond best and which patients are likely to benefit from this treatment.
Although not yet ready for clinical trials in humans, researchers are also working alongside a team of vets at Nihon University's School of Clinical Veterinary Medicine in Japan to treat pet dogs with naturally occurring brain tumours. Glioblastoma belongs to a group of brain tumours called gliomas, which can also affect dogs – and with an equally poor prognosis. So, this unique project will also monitor and offer the IL-12 treatment to dogs with gliomas, with their owner's consent, when no other treatment option is available.
Using the research gleaned from both the laboratory and veterinary hospitals, Dr Ishihara's team will observe the benefits and efficacy of the treatment, aiming to pave the way for future human clinical trials.
Emma Thompson, Head of Research at The Brain Tumour Charity, which is funding this project, said: "Our Quest for Cures grants are offered to the very best researchers in the field and are focussed on improving the lives of those with this devastating diagnosis.
"Finding new and innovative ways to treat glioblastoma is the only way we are going to move closer to a cure for this aggressive brain tumour. Exploiting the things we do know about glioblastoma – such as its use of collagen as an energy source for the cells – and targeting treatments like the collagen binding IL-12 has shown promise, and we hope that it will have clinical benefits for patients."
Hopes for childhood brain tumours
Imperial scientists are also involved in a separate, five-year, £1.5 million project for the Brain Tumour Charity's 'Quest for Cures'. This focusses on paediatric-type diffuse high-grade gliomas – some of the most aggressive brain tumours with the poorest prognosis.
Only between two and 15 per cent of children will survive for five years after diagnosis with this type of tumour, because current treatment options are limited to radiotherapy, which has limited success. The project team will be exploring the role of senescent (non-growing) cells in childhood brain tumour development and recurrence, in the hope of finding ways to target them with novel treatments.
New treatments are desperately needed as traditional cancer treatments target rapidly growing cells, but senescent cells are not growing, so those treatments do not eliminate them. However, senescent cells produce a vast number of biologically active molecules that can promote cancer cells to divide more rapidly and help the cancer to hide from the immune system. The Quest for Cures grant will help the team understand how senescent cells promote tumour development and explore how current senolytics – drugs that target senescent cells – can be adapted specifically to treat this group of childhood brain tumours.
The project is led by researchers from University College London and includes partners at the University of Cambridge and the Institute of Cancer Research (Sutton), as well as Imperial College London.
Research projects such as these aim to improve treatments for people like Jay Hellis, from Essex, who was diagnosed with a glioblastoma when he was just 19
Jay's story
Jay has responded well to treatment, but it has been a long road to recovery since his diagnosis in September 2021.
His first symptoms were headaches and loss of peripheral vision which his GP put down to migraines. Not happy with this diagnosis, Jay and his family took him to A&E at the Princess Alexandra Hospital in Essex for a scan.
Jay's mum, Toni O'Callaghan said: "After waiting for 10 hours, the results came back that Jay had a brain tumour. We were heartbroken. We had no knowledge about brain tumours, but we were glad we followed our guts and pushed to find out what was wrong with Jay."
An operation to remove as much of the tumour as possible was scheduled immediately.
After nine hours of surgery the mass was removed, but just 13 days later the family received the devastating news that tests showed it was a glioblastoma – the most aggressive brain tumour.
After surgery, treatment included six weeks of radiotherapy and 20 gruelling months of chemotherapy. Jay coped but was left with severe fatigue and other challenges affecting his memory and vision.
Despite this, Jay is trying to rebuild his life with support from his friends and family."
Jay has regular scans to monitor his tumour and he and his family praise the care he received and thank the vital research into brain tumours that has allowed Jay to be here today.
