A combination of two types of immunotherapy drug has produced promising results in brain cancer mouse models.

The study, carried out by researchers at the Children’s Hospital of Eastern Ontario (CHEO) in Ottawa, Canada, found that combining a type of immunotherapy called an SMAC Mimetic with another called an immune checkpoint inhibitor (ICI) produced an amplified anti-cancer effect in glioblastoma.

The team combined two SMAC Mimetics called LCL161 and Birinapant with two ICIs – one targeting a molecule called PD-1 and another targeting CTLA-4.

The result was a far greater anti-cancer effect than using either type of immunotherapy alone.

“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. Robert Korneluk, senior scientist at the CHEO Research Institute.

The findings represent an interesting new strategy for pharma companies to explore as PD-1 inhibitors, like Opdivo and Keytruda, and CTLA-4 inhibitors like Yervoy are already producing exciting results.

Both Opdivo and Keytruda belong to a class of drugs that prevent the activation of the PD-1 receptor situated on the surface of immune system cells. Given the activation of this receptor by cancer cells prevents their destruction, inhibiting the receptor’s activation reveals cancer cells to the immune system, allowing for their destruction.

Yervoy on the other hand targets CTLA-4 – a receptor that suppresses the activity of a set of cancer-killing immune cells called cytotoxic T-cells.

SMAC Mimetics mimic the activity of a protein called SMAC which, in cancer cells, is regularly downregulated. SMAC inhibits a set of molecules called inhibitors of apoptosis (cell death) proteins which leads to a greater chance of cell death.

The combination of PD-1 and CTLA-4 inhibitors with SMAC Mimetics, therefore, creates a dual-action therapy, increasing the visibility of cancer cells whilst enhancing their chances of cell death.

Even more intriguing than the combination’s success in glioblastoma – a notoriously hard-to-treat form of cancer – is the fact that it also proved highly effective in breast cancer and multiple myeloma.

According to Eric Lacasse, a scientist at the CHEO Research Institute, two drug companies are already testing the combination in human clinical trials begun this year. “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.”