Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Jun Ishihara, Imperial College London
Award: £299,991.32
Awarded July 2023
Paediatric high-grade glioma (PHGG) is the common type of childhood brain tumour. Despite aggressive treatments, most patients do not survive for longer than two years past diagnosis. This is due to the cancer developing resistance to treatment, showing the desperate need for effective new treatment options.
The recent introduction of immunotherapy has helped prevent cancers coming back after treatment, or spreading to other locations, in a number of cancers. Immunotherapy activates a patient’s own immune system to hunt down and kill the cancer cells. However, PHGG responds poorly to current standard immunotherapies for a number of reasons, such as not being able to activate the immune system, the cancer being resistant, or because it is hard to get the drugs to where they are needed.
Dr Jun Ishihara at Imperial College London has developed a new type of tumour-specific immunotherapy that he believes could be a breakthrough for patients with PHGG, especially when the cancer has come back after treatment.
His treatment uses a promising immunotherapy protein called interleukin-12 that is known to help immune cells find and kill several types of cancer cells. Despite being good at attacking cancer, interleukin-12 can be toxic in its original form and so could not be used on its own to treat cancer.
Dr Ishihara’s team have found that several cancers, including glioma brain tumours, use a lot more of the collagen protein compared to normal tissue. They edited their immunotherapy treatment so that it could bind to collagen proteins. This means that the toxic interleukin-12 will be directed at just the cancer cells because the immunotherapy proteins have bound to the collagen on the cancer cell. This reduced side effects and appears to be effective in lots of cancer types in the lab.
In this project, Dr Ishihara plans to test his new treatment in model systems which mimic the way the complex human immune system would respond to the treatment, not just whether the immunotherapy can kill cancers cells. He also wants to find a way to improve the way this immunotherapy gets into the brain where it is needed. Dr Ishihara hopes that this work will lead to the development of new and effective immunotherapies for PHGG patients and aims to bring the treatment to clinical trials within five years.