Ottawa researchers kill brain cancer in mice with combination immunotherapies

(L to R) Drs. Eric Lacasse, Shawn Beug and Robert Korneluk

OTTAWA, ON –A team of researchers at the Children’s Hospital of Eastern Ontario (CHEO) have published new data in Nature Communications showing that a promising combination of immunotherapies can deliver a one-two punch to brain cancer tumours in mice leading to high cure rates.

As part of their study, Drs. Eric Lacasse, Shawn Beug and Robert Korneluk found that a combination of drugs known as SMAC Mimetics and immune checkpoint inhibitors (ICIs) were able to amplify the kill rates of cancer tumour cells, while at the same time discovering a new mechanism by which the combination promotes long-term immunity against glioblastoma tumours.  According to the researchers, the combination therapy also proved to be highly effective against breast cancer and multiple myeloma.

“These findings represent a significant evolution in our research and the field of immunotherapy…we are the first in the world to show the synergistic tumour-killing impact of combining SMAC Mimetics with immune checkpoint inhibitors for glioblastoma,” said Dr. Korneluk, who is a distinguished professor at the University of Ottawa and senior scientist at the CHEO Research Institute. “You could say it takes two to tango, that it takes a combination strategy to impact cancer cure rates,” he adds.

In 2014, a team of scientists led by Dr. Korneluk discovered that combining SMAC Mimetics with immune stimulators, or live virus therapies, had a synergistic or amplified tumour-killing effect that was greater than either agent on its own. These latest findings show that SMAC Mimetics also have a powerful synergistic effect with ICIs, which are relatively new drugs that are showing great promise in the clinic.

As part of this latest study, SMAC Mimetics known as LCL161 and Birinapant were combined with ICI antibodies targeting PD-1 and CTLA-4 immune checkpoints.

“Two drug companies have initiated human clinical trials this year to assess the impact of this combination of SMAC Mimetics and ICIs on patients with a variety of cancers,” said Lacasse, a scientist at the CHEO Research Institute.

Although it could be years before any clinical trials begin for adults or children with the deadly brain cancer, glioblastoma, he says the research team is looking forward to seeing how scientific evidence from these experimental treatments adds to our knowledge. “It’s an exciting, exploratory field and we hope we’ve hit a home run,” he said.

“This research heightens our understanding of the mechanics behind this double-whammy effect, which both enhances the immune response and weakens tumour cells to immune attack,” said Beug, lead author of the 2014 and 2017 papers. “We’re hoping that more oncologists and biotech companies test out this combination in clinical trials as we continue to decipher how SMAC Mimetics encourage the immune system to kill cancer cells.”

The research was funded by the Canadian Cancer Society Research Institute, Brain Canada (with financial support from Health Canada through the Canada Brain Research Fund) and the Canadian Institutes of Health Research. In addition, the work was supported by donations to the Ottawa Regional Cancer Foundation, the Kiwanis Medical Foundation and the CHEO Foundation.

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