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Developing a cancer vaccine to treat children with aggressive brain cancers

Malignant brain tumours are the leading cause of cancer death in children. Amongst these, pediatric high-grade gliomas (HGGs) – a group of cancers that include glioblastoma multiforme, anaplastic astrocytoma, and diffuse intrinsic pontine glioma – are the most aggressive. Treatments for HGGs are both ineffective and highly toxic, meaning that sadly, most children diagnosed with these cancers succumb to their disease within a year of diagnosis.

New hope is desperately needed for these children, which is why Dr. Taha Azad, a synthetic biologist and cancer researcher at the Université de Sherbrook in Quebec, will use new funding from a Terry Fox New Investigator Award to search for innovative ways to treat these deadly cancers.

“Current therapies for pediatric HGGs are clearly not good enough,” says Dr. Azad. “And unless we start to think outside of the box, it will be very difficult to bring new hope to these children and their families.”

Over the next three years, Dr. Azad will receive $442,193 to help make a difference. His Terry Fox New Investigator Award project will focus on harnessing the power of the immune system to fight HGGs by recruiting an unlikely ally: viruses.

“Over the last 10 years, it has been proven that specific viruses – known in the cancer world as oncolytic viruses – can be used to activate the immune system to fight cancers,” explains Dr. Azad. “These viruses have been shown to be effective and safe in adults. Now, we want to see if it’s possible to prove the same thing in children with HGGs.”

According to Dr. Azad, HGGs are a good candidate for this research because they are “cold tumours.” This means that they have specific features that allow them to hide from the immune system, which does not recognize them as foreign entities and, therefore, does not send cells to fight them off.

Oncolytic viruses reverse this process by making tumours “hot”. They bind to tumour cells and proliferate exclusively within them, creating so much activity that they alert the immune system of the tumour’s existence. As immune cells flood towards the areas surrounding the tumour, these viruses can attract specific immune cells into the tumour, which eventually destroy both the virus and the cancerous cells.

The TFRI-funded Canadian Oncolytic Virus Consortium — a group of world-leading immunologists who will mentor Dr. Azad in this project — has already conducted 13 clinical trials proving the efficacy and safety of oncolytic viruses for some hard-to-treat adult cancers. They will now work with Dr. Azad to see if this research can be expanded for use in children.

“Pediatric cancers are very different from adult cancers, and children are far more susceptible to the adverse side effects of current treatments than adults,” explains Dr. Azad. “That’s why the main goal of this project is first and foremost to see if we can create an oncolytic virus for HGG that is both effective and safe in children.”

Dr. Azad’s hope is that this can be achieved within the next three years, setting the stage for this research to move into clinical studies soon after the culmination of his New Investigator Award.

“Ultimately, we would like for this research to make its way into the health system so it can help save the lives of children diagnosed with deadly cancers,” he says. “This project is a hugely important step in the journey towards that.”