A new class of therapies called SMAC mimetics could work in conjunction with immune checkpoint inhibitors to treat brain cancer patients, according to a study.
SMAC mimetics block the activity of proteins that prevent cell death while sensitizing tumors to allow immune cells to attack them.
The use of SMAC mimetics, in combination with immune checkpoint inhibitors, has shown high cure rates in mice, researchers said.
Their study, “Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma,” was published in Nature Communications.
“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,” Dr. Robert Korneluk, a distinguished professor at the University of Ottawa and senior scientist at the CHEO Research Institute, said in a news release. “You could say it takes two to tango. We believe that it takes a combination strategy to impact cancer cure rates.”
SMAC mimetics work by inhibiting the function of proteins that help cancer cells avoid immune attack and evade death.
In a 2014 study, Korneluk’s team found that combining SMAC mimetics with immune stimulators or live virus therapies produced stronger anti-tumor activity than either agent alone.
They have now learned that SMAC mimetics can work with immune checkpoint inhibitors — either PD-1 or CTLA-4 targeting antibodies — to cure mice with glioblastoma, the most common type of brain cancer. SMAC mimetics and immune checkpoint inhibitors that were administered as a single agent were ineffective in the mice.
“Two drug companies have initiated human clinical trials this year to assess the impact of this combination of SMAC Mimetics and immune checkpoint inhibitors on patients with a variety of cancers,” said Eric 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, we’re 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.”
“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 Shawn 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.”
