CHILDHOOD CANCER RESEARCH
Developing new immunotherapy strategies to overcome barriers in glioblastoma treatment
A/Prof Orazio Vittorio
A/Prof Orazio Vittorio’s 2024 grant is generously funded by the Melissa Lewis Foundation for the third year.
He is the Head of the Metal Targeted Therapy & Immunology (MTTI) lab based at the University of New South Wales (UNSW Sydney) and Team Leader at the Children’s Cancer Institute.
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!”
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 effects of copper found in neuroblastoma and in high-grade gliomas.
Glioblastoma
Brain tumours are the leading cause of disease-related death in children and are the second most diagnosed cancer in childhood.
Glioblastoma is a lethal type of brain cancer that has an incredibly poor prognosis despite aggressive approaches to treatment. Its notorious ability to infiltrate and invade the primary brain tumour’s surrounding healthy tissue makes complete eradication nearly impossible. Consequently, glioblastoma patients typically face a survival period of approximately 15 months.
Over the last 30 years, the abysmal 5-year survival rate has failed to increase significantly, now at below 5%. More importantly, current therapeutics available in the clinic can cause both short and long-term side effects that severely affect a patient’s quality of life.
Associate Professor Orazio Vittorio’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 Vittorio has dedicated much of his research to 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.
Now, in this Cure Cancer-funded project, he is investigating the presence of extrachromosomal DNA (eccDNA) in glioblastoma and its instrumental role in causing a tumour to spread and hamper immune response. EccDNA are small, circular DNA molecules found in tumour cells that exist separately from chromosomal DNA, and are present in approximately 40% of cancer lines.
The primary objective of this novel research is to provide a comprehensive understanding of the creation and movement of eccDNA in tumour and immune cells, with a specific focus on the involvement of copper in this process. These findings will enable Orazio and his team to develop a world-first therapeutic strategy to target and eliminate eccDNA in glioblastoma patients’ tumour and immune cells, and reduce cancer progression.
The impact of funding on the future of childhood brain cancer research
Through the support he’s received from Cure Cancer and our generous donors since 2018, Orazio and his team are now working on clinical trials for his previously-funded research on combining copper chelation therapy with other immunotherapies.
“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, who can really have an impact on the lives of people in Australia and worldwide.”
With the grant extension from The Melissa Lewis Foundation, Orazio hopes his groundbreaking research will set a benchmark for future treatment of childhood brain cancers. Ultimately, his findings will pave the way for personalised medicine in glioblastoma and improve the lives of children with this devastating diagnosis.
