A/Prof Orazio Vittorio’s clinical trial is supported by a generous donor
He is the Head of the Metal Targeted Therapy & Immunology (MTTI) lab based at the University of New South Wales (UNSW Sydney).
A/Prof Orazio Vittorio’s impressive body of work on neuroblastoma has moved into clinical trials. Thanks to the support of our generous donors since 2018, Orazio and his team are now undertaking a world-first, international study based on his previously-funded research on combining copper chelation therapy with other immunotherapies.
This year, Cure Cancer is also supporting Orazio’s project on reprogramming neutrophils to improve CAR-T cell therapy for neuroblastoma.
Neuroblastoma: A devastating childhood cancer
Neuroblastoma is one of the most aggressive types of childhood cancer, mostly affecting children aged 0-5, with an average 5-year survival of 50% for high-risk cases.
Due to the toxicity of current treatments, a third of children who have survived neuroblastoma experience life-long side effects like hearing loss, infertility and an increased risk of developing a secondary cancer.
Sadly, children whose high-risk neuroblastoma has relapsed (where the cancer has returned) face a very poor long-term chance of survival, at less than 10%. There is an urgent need to identify and trial novel therapies and approaches that have fewer side effects.
Copper chelation therapy: A breakthrough treatment for neuroblastoma
In 2018, Orazio and fellow Cure Cancer alumna Prof Maria Kavallaris made the groundbreaking discovery that removing copper from the blood – using copper chelators, a clinically approved treatment for Wilson’s disease – enables the immune system to target and destroy some of the deadliest cancers that are resistant to immunotherapy.
By repurposing an existing drug typically used to manage excess copper levels in the body, as seen in the children's genetic disorder Wilson’s disease, it is possible to redistribute copper within neuroblastoma tumours. This not only makes neuroblastoma cells more visible to the immune system but also strengthens cancer-fighting immune cells, enabling them to proliferate and infiltrate tumours.
Orazio and his team have found that paired with conventional chemo-immunotherapy (anti-GD2 antibody therapy combined with chemo), copper chelation therapy could improve long-term survival rates for children with relapsed neuroblastoma from 10% to 50%, a finding that was recently published in Nature Communications.
Hope for neuroblastoma patients: A world-first clinical trial
A/Prof Orazio Vittorio’s ‘ENHANCE’ feasibility pilot study aims to determine if a novel combination therapy using copper chelation therapy (trientine tetrahydrochloride) and chemo-immunotherapy (dinutuximab-beta, irinotecan and temozolamide) is safe and tolerable in children with relapsed, high-risk neuroblastoma.
Commencing in 2025, the study will recruit 10 patients from across Australia in collaboration with Dr Toby Trahair from the Sydney Children's Hospital and the ANZCHOG (Australia and New Zealand Children's Haematology/Oncology Group), and is expected to run for around five years, with ongoing follow-up with patients over the subsequent years.
As copper chelation medication is widely used in children and has few side effects, Orazio and his team anticipate that it can be safely combined with chemo-immunotherapy and will enhance the effectiveness of treatment for relapsed neuroblastoma. If they are successful in proving the safety of their cutting-edge treatment approach, they will proceed to test the effectiveness of the therapy through the international BEACON2 study, a larger clinical trial based in Europe.
Ultimately, Orazio hopes that his groundbreaking research will set a benchmark for future treatment of childhood neuronal cancers. His findings will pave the way for personalised medicine and improve the lives of children with this devastating diagnosis.