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Delivering a new combination therapy for glioblastoma

Project details

Researcher
Professor Khuloud Al-Jamal
Institute
King's College London
Research area
Brain tumours
Funding type
Project grant
Awarded in
September 2020
Completion
Ongoing

Overview

Glioblastoma is one of the deadliest human cancers, with most patients surviving just 12 to 15 months from diagnosis. There is no treatment that is effective in the long-term.

Professor Al-Jamal and colleagues aim to develop a new treatment that combines chemotherapy and immunotherapy techniques, and to deliver this treatment directly to the tumour using a new delivery method to cross the blood-brain barrier.

Following rigorous assessment as part of our competitive grant round, this project was recommended for its strong potential to advance treatment of glioblastoma. The multi-disciplinary team combines expertise in nanotechnology, immunology, neurosurgery, and clinical trial development, making them well-placed  to succeed in their aim to deliver a novel therapy in this area of great need.  

About glioblastoma

Glioblastoma is the most common primary brain cancer in adults, with around 2,500 cases diagnosed every year in the UK.

It is a grade four tumour, meaning that it grows and spreads quickly, and it infiltrates the brain, wrapping finger-like tentacles around vital brain structures, which makes complete surgical removal impossible.

The current treatment strategy includes surgery to remove as much tumour as possible, followed by radiotherapy and chemotherapy to destroy remaining tumour. This prolongs survival but is not curative. Only a quarter of patients survive more than a year from diagnosis.

The need for new treatments is urgent.

Read more: About brain tumours

Delivering a new combination therapy for glioblastoma

Professor Al-Jamal and colleagues aim to develop a new treatment that combines chemotherapy and immunotherapy techniques, and to deliver this treatment directly to the tumour using a new delivery method to cross the blood-brain barrier.

The blood-brain barrier is a natural filter than protects the brain from harmful substances in the blood. It complicates the treatment of brain tumours – and other brain disorders – because it hampers the delivery of therapeutics to the brain. It is a major cause of the lack of progress in the treatment of brain tumours.

The team will use a class of chemotherapy drugs known for their ability to trigger a specific mechanism of cell death known as immunogenic cell death (ICD). During ICD, the cancer cells secrete a substance that attracts immune cells to engulf them.

In combination with these drugs, they will use gene silencing approaches that essentially switch off a ‘don’t eat me’ flag that cancer cells use to evade clearance by the immune system. Switching off this flag removes this protection and it is expected that the co-delivery of the ICD drugs and the gene silencer will make the tumours highly susceptible to clearance by the immune system.

To ensure that both treatments can cross the blood-brain barrier and reach cancer cells at high concentration, the team will use nanocarriers 10,000 times smaller than a human hair to deliver the treatment.

The team will first perform tests against brain cancer cells and stem cells to identify the most effective combination of drugs. The essential next stage will be to test the therapy in mice, to see how it works in a living system. To mimic what happens in real patient scenarios, they will administer treatment after tumours have been surgically removed.  

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Impact

Glioblastoma is one of the devastating forms of cancer. It has no treatment that is effective in the long-term, and most patients die within 12 to 15 months of diagnosis.

There is a desperate need for new treatments for glioblastoma and we hope that Professor Al-Jamal's research will succeed in delivering a new treatment option that can progress through to clinical trial.

“The project is of paramount importance in the fight against brain tumours. Although immunotherapies have produced ground-breaking results in the treatment of numerous solid tumours, they are yet to produce significant survival benefits for patients with brain tumours. This is in part due to the exclusion of large therapeutic molecules by the blood-brain barrier, but also due to a lack of effective combination immunotherapies. The current proposal addresses both of these impediments in an innovative manner that stands a very good chance of success.” Reviewer

About the research team

Professor Khuloud Al-Jamal is Chair of Drug Delivery and Nanomedicine  and Head of Medicine Development at King’s College London. Her work includes pre-clinical translation of nanomedicine, with special interests in brain diseases and cancer.

In this cross-school collaboration, Professor Al-Jamal brings together a strong multi-disciplinary team, including Dr Julie Wang, Dr Adam Walters and Dr James Arnold as co-investigators. They are collaborating with neuro-surgeon Professor Keyoumars Ashkan, who will provide the clinical patient samples required for the project.  

“The team is world-leading. Their strength lies in synergistic expertise in drug delivery and cancer therapeutics between the Wang and Al-Jamal laboratories.” Reviewer

Related projects

Brain tumours are one of our current research priorities, reflecting the large unmet need in this area. Our aim is to fund research to advance understanding of the causes and underlying mechanisms of brain tumours, and help us to diagnose and treat them more effectively.

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