Professor Michael Brown was well into his career when he first turned his research toward brain cancer.
After specialising in both medical oncology and clinical and laboratory immunology, a South Australian research grant required a focus on diseases with poor prognosis, leading him to glioblastoma — the most common and deadliest brain cancer. He joined Brain Cancer Australia's National Consortium of leading experts not long after – in 2018.
“Brain cancer is an awful disease,” he says. “It’s confined to the organ that makes us who we are, and when it goes wrong, the effects are devastating – it eats away at our personhood.”
As the Head of the Translational Oncology Laboratory at the Centre for Cancer Biology in South Australia, Michael was motivated to look for new treatments for glioblastoma because “the current treatment is not at all satisfactory.”
“Brain cancer is confined to the organ that makes us who we are, and when it goes wrong, the effects are devastating – it eats away at our personhood.”
Around the time of the grant ten years ago, a single case published in the New England Journal of Medicine showed a complete—but temporary—response of a recurrent glioblastoma patient to CAR-T cell therapy. This treatment involves re-engineering a patient’s own immune cells so they can better recognise and attack cancer.
“That was a striking finding, and the report energised the field,” Michael recalls. “It made me think seriously about bringing CAR-T cell therapy into brain cancer trials.”
He was already completing the first Australian CAR-T cell trial in patients with solid cancer including melanoma when he turned to apply the same technology in brain cancer patients. He leads the trial for adults with recurrent glioblastoma at the Royal Adelaide Hospital. His colleague Professor David Ziegler at Sydney Children’s Hospital runs another study for children with a rare tumour known as diffuse intrinsic pontine glioma (DIPG). “We make the CAR-T cell products in Adelaide for patients in both trials,” he explains.
“What attracted me to immunology was that it was a black box full of possibilities. You could manipulate the immune system to create better therapies.”
Like many in his field, Michael was drawn to oncology because he wanted to make a difference through treatment. He found that possibility expanded even further in immunology. “What attracted me to immunology was that it was a black box full of possibilities,” he says. “You could manipulate the immune system to create better therapies.”
Inspired by cancer immunotherapy pioneers Steve Rosenberg at the US National Cancer Institute and Malcolm Brenner at St Jude Children’s Research Hospital, Michael went on to train in cell and gene therapy research at St Jude in the United States and completed a PhD in cancer immunotherapy. “That experience solidified my interest in marrying immunotherapy with cancer medicine.”
Today, his work in Adelaide is focused on a CAR-T cell trial with nine patients who have been given their own CAR-T cells intravenously. The next phase will deliver cells directly into the brain through the intracerebroventricular (ICV) route - meaning they are placed into the brain’s fluid-filled spaces rather than given through the bloodstream. "After that, we plan to boost the cells’ activity with a natural protein that helps immune cells grow and stay active, in collaboration with Baylor College of Medicine in Houston.”
For Michael, progress comes through persistence. “We need a paradigm shift away from chemotherapy and radiation,” he says. “My hope is that experimental therapies like CAR-T cells can gain a greater foothold.”
Measuring impact is still evolving. “The best outcome would be to see clearer improvement than what we’re seeing now,” Michael explains. “We’re picking up some activity in the blood and on MRI, but it’s difficult to interpret.” His team is now incorporating FET-PET imaging — a way to assess tumour viability more directly — into the next protocol amendment. “That will give us a better handle on how effective the therapy really is, because MRIs alone don’t tell the full story.”
Michael says collaboration is key to progress. “Our gene-transfer vectors come directly from Baylor, and we couldn’t do this work without their technology,” he says. “Here in Australia, we work with teams at Sydney Children’s Hospital, the Children’s Cancer Institute, the Walter and Eliza Hall Institute, and others. It takes many disciplines working together — and when people come from quite different backgrounds, that fusion of expertise allows us to achieve things none of us could do alone.”
“That’s the advantage of an organisation like Brain Cancer Australia — it can draw people together across the country, sharing techniques, tissue samples and knowledge to advance the field.”
As a member of Brain Cancer Australia’s National Consortium, Michael is also committed to the development of national research infrastructure — the systems and collaboration needed to make progress possible. “We have a relatively small population, and it’s widely distributed, so it’s absolutely necessary that we work together and share resources,” he says. “That’s the advantage of an organisation like Brain Cancer Australia — it can draw people together across the country, sharing techniques, tissue samples and knowledge to advance the field.”
What keeps him motivated is simple. “It’s the prospect that you might make a difference,” he says. “It’s a long game and the changes are incremental. Our patients in the trial are generous — they know this treatment is experimental and may not help them directly, but they still join our studies. That courage reminds us why the work matters.”
