Developing new immunotherapy strategies to treat glioblastoma

A/Prof Orazio’s grant is generously funded by the Melissa Lewis Foundation for the second year.

He is a Project Leader of the MTTI (Metal Targeted Therapy & Immunology) lab based at the University of New South Wales.

A/Prof Orazio Vittorio completed his PhD in Oncology at the University of Pisa in February 2011, during which he was diagnosed with kidney cancer.

“I was lucky the tumour was found when it was small, so my chances of survival were good,” he says.

“It gave me more reasons to put all my efforts into cancer research. In 2011, I became a father and decided to focus my research in finding better cures for childhood tumours like neuroblastoma. Children are our future!”

A/Prof Orazio’s body of work aims to understand the biology of aggressive childhood cancers so that he can develop more effective therapeutics and improve the quality of life and survival of children with cancer. He was the first scientist to discover the immunosuppressive activity of intra-tumoral copper in neuroblastoma and in high-grade gliomas.

Glioblastoma

Brain tumours are the leading cause of disease-related death in the paediatric population and are the second most diagnosed cancer in childhood.

The survival rate for glioblastoma remains abysmal at below 5% over 5 years and has failed to increase significantly over the last 30 years. More importantly, current therapeutics available in the clinic are often associated with both short- and long-term side effects that can severely affect a patient’s quality of life. The failure in developing novel treatment strategies for glioblastoma can be attributed to the barriers within the glioblastoma microenvironment.

A/Professor Orazio's research

Over the last decade, it has been demonstrated that our immune system has the potential to eliminate tumours, including brain tumours, if appropriately stimulated. Unfortunately, current immunotherapies have provided only limited clinical benefit against brain tumours as these tumours have developed the ability to remain undetected from the immune system.

A/Prof Orazio is now focused on overcoming this limitation and developing a new way to increase the ability of the patient’s immune system to counter glioblastoma by combining both copper chelation therapy with immune checkpoint and CAR T immunotherapies.

Copper chelators have been used extensively for over 40 years, particularly for treating a disorder known as ‘Wilson’s Disease’. It is known to be less toxic to patients and have few adverse effects in both adults and children.

This research project will investigate a new strategy to target the tumour microenvironment in glioblastoma. It also represents a potentially viable treatment regimen in which copper may stimulate the immune system to enable it to fight against the tumour.

The extensive use of copper chelators in the clinic currently and in conjunction with previous work by A/Prof Vittorio’s research group has led the team to believe that copper chelators can be viably repurposed as anti-cancer agents. These copper chelators are affordable and already have regulatory approval in both Australia and the US, which makes it a promising new treatment.

The impact of funding on the future of childhood brain cancer research

Through the support he’s received from Cure Cancer and its generous donors over the last four years, A/Prof Orazio and his team are now working on clinical trials. This ground-breaking research will offer pathways to more accessible treatment than standard therapies for glioblastoma, with less risk of side effects. ­­

With the grant extension from The Melissa Lewis Foundation, A/Prof Orazio hopes this research will provide the necessary foundation to support future clinical trials investigating copper chelators in glioblastoma patients.

“Cure Cancer is doing great work not only for science, but also for scientists in this country. Because of you, there are scientists who are not leaving the country, who are not leaving their jobs, that can really have an impact in the lives of Australian people and also worldwide.”

Together, we can cure cancer.

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