Researchers at WEHI have identified a promising new two-in-one treatment that not only targets and destroys an aggressive form of brain cancer, but also helps the immune system develop a lasting defence against it.
This dual-action approach uses a specific immunotherapy known as CAR T cell therapy to treat gliomas, an incurable brain cancer with few treatment options.
The pre-clinical findings have revealed the therapy’s ability to eliminate glioma cells and its potential to strengthen the immune system to prevent future tumour growth – two significant advances that could revolutionise the way these lethal cancers are treated in the future.
Their cutting edge new immunotherapy not only targets and destroys an aggressive form of brain cancer, but also helps the immune system develop a lasting defence against it.
“CAR T cell therapy is clever because it uses a patient’s own immune cells and engineers them to recognise and kill the tumour, with no long-term side effects,” Prof Jenkins said.
The discoveries provide fresh hope for patients, not just for a cure, but for more precious time. We’re excited to see where this incredible research will lead.
Survival rates for gliomas, an aggressive tumour, have barely improved in 30 years, but Misty and her team hope this “two-in-one” therapy that “completely cured” “100 per cent” of mice during trials could change this.
CAR T cell therapy is an innovative new approach that involves isolating a patient’s immune cells, engineering them to become “super killer cells” and then re-infusing them into the patient to fight their cancer.
While CAR T cell therapy has shown promise for brain cancer treatment, finding the right proteins to target on brain cancer cells has been a major hurdle.
The WEHI-led study has revealed a protein called EphA3, found on the surface of high-grade glioma cells, could be a key target for CAR T cell therapy.
Professor Misty Jenkins said many treatments that succeed in preclinical trials failed in humans, but these strong results gave her confidence.
“This therapy not only targeted and killed the cancer cells, but also triggered a long-lasting immune response preventing future tumour growth,” she said.
“We never expected a two-in-one breakthrough that could offer such lifesaving possibilities.”
The breakthrough was in CAR T cell therapy, considered the future of cancer treatment but currently limited to just a few select types, and treated adult and paediatric tumours.
The team hopes brain cancer patients can trial it within two years.
Prof Misty said radiation and chemotherapy were like using a “blunt instrument” to kill cancer, but CAR T cell therapy took “treatment to a new paradigm”.
“We can specifically target the tumour cells only and leave the healthy cells unharmed,” she said.
But in order to target the cancer, Prof Misty said they have to find a unique feature, a red flag or beacon that says “tumour over here”. “As soon as we know what those red flags are … it’s very easy for us to design drugs for them now,” she said.
“We can take the patient’s blood out of a patient, engineer it and give them the right glasses.” “Then the patient’s own T cells … can kill their own tumour.”
She said they had discovered a protein in the brain tumours that wasn’t “expressed in other healthy parts of the body”, so made T cells that recognise it. “They then direct the immune system to recognise and destroy the brain tumour.”
She said their study, published in Journal of Immunotherapy of Cancer, found this protein, EphA3, was also in the blood vessels that line the tumour, so they could “melt the tumour from within”.
She said their CAR T cells were so effective they “hung around” afterwards, ready to attack returning cancer cells – like a vaccine – and prevent relapse, a potential “game-changer”.
“In the mice, when we gave them [new] brain tumours, they actually were able to also cure those brain tumours as well.” “The potential to revolutionise brain cancer treatment – like what has been achieved for other cancers – makes this a truly exciting time,” she said.
“We stand on the brink of transforming brain cancer treatment.”
WEHI PhD student researcher Leesa Lertsumitkul was first author.
Melbourne dad Toby Ewert, 46, who was diagnosed with brain cancer in 2020, said research like this could be the reason someone gets more time with family.
“It makes a huge difference to the patient, but it probably makes a bigger difference to everyone else around them,” he said.
“Five extra years … that might be the difference in meeting grandchildren.
“But if researchers don’t get enough funding, it’ll just take longer.”
This study was proudly funded by The Brain Cancer Centre with other partners including the National Health and Medical Research Council (NHMRC), Robert Connor Dawes Foundation, Isabella and Marcus Foundation, Medical Research Future Fund (MRFF), Cure Brain Cancer Foundation and Zoe’s Fight Foundation.
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