Combination Immunotherapies Successful in Glioblastoma

SMAC mimetics and immune checkpoint inhibitors, together, promote tumor immunity against deadly brain cancer.

A combination treatment of SMAC Mimetics plus immune checkpoint inhibitors (ICIs) creates a powerful synergistic tumor-killing effect against glioblastoma, according to a study published in Nature Communications.

“These findings represent a significant evolution in our research and the field of immunotherapy, said senior scientist Dr Robert Korneluk. “We are the first in the world to show the synergistic tumor-killing impact of combining SMAC Mimetics with immune checkpoint inhibitors for glioblastoma. You could say it takes 2 to tango. We believe that it takes a combination strategy to impact cancer cure rates.”

The combination therapy was also shown to be highly effective against breast cancer and multiple myeloma, according to the authors.

In 2014, the investigative team found that combining SMAC Mimetics with immune stimulators or live virus therapies had a synergistic or amplified effect that was stronger than either agent alone. In the current study, the investigators showed that SMAC Mimetics have a powerful synergistic effect with ICIs in mice.

For the study, investigators combined the SMAC Mimetics LCL161 and Birinapant with ICI antibodies that target 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 Eric Lacasse, 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 add to our knowledge. It’s an exciting, exploratory field and we hope we’ve hit a home run.”

The lead author of both studies Shawn Beug added, “This research heightens our understanding of the mechanics behind this double-whammy effect, which both enhances the immune response and weakens tumor cells to immune attack. 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.”