Cancer research: New treatment for aggressive tumours
A group of Canadian and American scientists has made a breakthrough in the search for life-saving brain cancer treatments.
The group, co-led by researchers at McMaster University in Hamilton, Ont. and the Hospital for Sick Children (SickKids) in Toronto, has developed a method for treating the most aggressive form of brain cancer: glioblastoma. The treatment uses the body’s own immune cells, called T cells, to target and destroy cancer cells in the brain.
It’s only been tested in mice so far, but Sheila Singh, co-senior author and director of McMaster’s Centre for Discovery in Cancer Research, is hopeful human trials could begin before 2030.
“In the next five years, I hope to see some movement of the next steps to move towards clinical trials,” she told CTVNews.ca in an interview over Zoom on Thursday.
Singh and her co-authors published their research in the scientific journal Nature Medicine on Friday.
50 per cent of tumours destroyed
The treatment was developed to target an aggressive type of brain tumour that recurs after a patient has been treated for an initial glioblastoma tumour with surgery, radiation therapy and chemotherapy.
While conventional cancer treatments might remove or shrink the initial mass, the tumours often return, Singh said, leaving patients with only months to live.
The method Singh and her team developed for treating these glioblastoma tumours destroyed them at least 50 per cent of the time in animal trials, and doubled survival time. And it doesn’t only work for glioblastoma.
“We thought, if this works so well in glioblastoma, which is a very invasive cancer, what about other cancers that invade the brain?” Singh said. “So we tried it out in our models of pediatric medulloblastoma, a very aggressive childhood cancer,” Singh said.
The treatment worked. It also worked when they tested it on cancer that had spread to the brain from elsewhere in the body, as opposed to cancer originating in the brain.
‘Soldiers of our immune system’
To develop their therapy, Singh and her team looked for features unique to the cancer cells that would give special, modified immune cells something to target.
They honed in on a protein called Roundabout Guidance Receptor 1 (ROBO1) that sits on the outside of the cell and helps direct the cell’s axon – a thin fibre that connects nerve cells so they can communicate.
“When you’re a baby and your brain is developing, your axons will lay out the map and they will actually guide the rest of the cells across to form the brain,” Singh said, “and in general, proteins that control axonal guidance are only active during brain development, like in fetuses and little babies.”
Singh said the team didn’t understand at first why they were seeing ROBO1 in adult brain cells. Eventually, they cracked the code.
“It turns out that it’s reactivated in cancers to help the cancers invade,” she said. “So it’s like (glioblastoma) is hijacking this known developmental pathway of axonal guidance to use it maliciously and badly to invade the whole brain.”
With their cancer cell marker identified, the team readied their cancer fighters: chimeric antigen receptor (CAR) T cells. CAR T cells are regular immune system cells that have been modified to hunt down and destroy a specific target.
“T cells are just killer … and if they latch on to a germ or a virus, they’ll kill that,” Singh said. “And if they latch on to a cancer cell, they’ll kill that.”
Singh and her team were able to shrink and sometimes destroy tumours in their animal subjects by extracting regular T cells from their blood, modifying those cells to give them the ability to find and attack ROBO1, and putting them directly into the brain. Once in the brain, the CAR T cells did exactly what the team hoped they would.
“So the cells that normally are the soldiers of our immune system that kill infections can now be armed against cancer,” Singh said.
Singh and her partners from the Princess Margaret Cancer Centre, the University of Toronto, the University of Virginia and the University of Pittsburgh worked for seven years to develop their treatment.
Some day, she hopes it can do for human cancer patients what it has done in animal trials.
“There are (glioblastoma) patients who are in desperate need of new therapeutic approaches. There’s a 96 per cent rate of people dying (within) five years,” she said. “We need to move quickly to get them better options.”
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