Novel Immune-Based Combination Therapies Successful in Treating Brain Cancer
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Combining a cancer-targeting virus with radiation to treat brain cancer in mice was more effective than either therapy on its own according to University of Alberta research, providing hope for new treatments that combine immunotherapy with traditional surgery, chemotherapy or radiation.
The researchers treated mice with glioblastoma brain tumours simultaneously with high-dose radiation and a genetically engineered oncolytic vaccinia virus, a virus that has been used safely as a vaccine against smallpox.
The researchers — who chose to target glioblastoma because it is among the deadliest cancers — saw a 15 per cent cure rate among the virus-treated animals and 20 per cent for those that received radiation alone. However, 67 per cent of the mice treated with both therapies were cleared of their tumours. The team also re-introduced fresh brain cancer cells to some of the cured mice and found that 62 per cent of the combination-treated mice were able to reject or resist new cancer.
“It was quite remarkable to see that the effect of the combination was greater than either of its parts alone,” says first author Quinn Storozynsky, a graduate research assistant fellow in the Faculty of Medicine & Dentistry who led the research as part of his PhD thesis.
“You need some way to seek and destroy cancer cells, so if you can harness the immune system, that's an incredible way to have this evolutionarily conserved response do the work for you,” he says.
“There aren't many therapies for cancer that work really well on their own because the nature of tumours is that they are not uniform due to high mutation rates, so combinations of therapies have the greatest chance of success,” says principal investigator Mary Hitt, associate professor of oncology.
Storozynsky says he would like to see further work done combining vaccinia or other oncolytic viruses with different doses of radiation to learn how to optimise the effect. Hitt suggests testing their combination with another immunotherapeutic agent known as an “immune checkpoint inhibitor,” which interferes with cancer’s anti-immune defence system, to see whether the effectiveness can be amplified even further.
Although only one oncolytic virus has so far been approved by the U.S. Food and Drug Administration for use in humans and the virus is not yet approved in Canada, Hitt sees more becoming clinically available within the next decade.
“It's a slow process of confirming the safety and effectiveness through clinical trials, but I think it's just a matter of time,” she says.
Reference: Storozynsky QT, Agopsowicz KC, Noyce RS, et al. Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model. Cancer Letters. 2023;562:216169. doi: 10.1016/j.canlet.2023.216169
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