Oncolytic virotherapy before surgery sensitizes TNBC to checkpoint therapy

Researchers have demonstrated that neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer (TNBC) to immune checkpoint therapy. The findings were recently published in Science Translational Medicine.

TNBC is a notoriously aggressive and difficult-to-treat type of breast cancer for which treatment options are few and associated with severe toxicities. Utilizing a therapeutic mouse model that mimics the metastatic spread of breast cancer after surgery, researchers have demonstrated that oncolytic virus therapy in combination with immune checkpoint blockade cured 60–90% of the mice, compared to zero for the checkpoint inhibitor alone and 20–30% for the virus alone.

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Lead author, Marie-Claude Bourgeois-Daigneault from the Ottawa Hospital Research Institute and University of Ottawa (both Canada) stated: “It was absolutely amazing to see that we could cure cancer in most of our mice, even in models that are normally very resistant to immunotherapy. We believe that the same mechanisms are at work in human cancers, but further research is needed to test this kind of therapy in humans.”

The team believe that their findings warrant oncolytic virus therapy in combination with immune checkpoint blockade testing as a neoadjuvant treatment option in the window of opportunity between TNBC diagnosis and surgical resection.

“Our immune system is constantly trying to recognize and kill cancer cells, but the cancer cells are always trying to hide from it,” explained study lead John Bell from The Ottawa Hospital and the University of Ottawa. “When you infect a cancer cell with a virus, it raises a big red flag, which helps the immune system recognize and attack the cancer. But in some kinds of cancer this still isn’t enough. We found that when you add a checkpoint inhibitor after the virus, this releases all the alarms and the immune system sends in the full army against the cancer.”

The research from both studies indicates the potential of viruses for enhancing the potential of checkpoint therapy and expanding it to new types of cancer.

Sources:

Bourgeois-Daigneault MC, Roy DG, Aitken AS et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy Sci. Trans. Med. doi: 10.1126/scitranslmed.aam7577 (2017) (Epub ahead of print); Eureka alert press release