Drs. Marie-Claude Bourgeois-Daigneault and John Bell.
Immunotherapy, which helps the body’s immune system attack cancer, has revolutionized treatment for cancers such as melanoma and leukemia. However, many other kinds of cancer remain resistant.
A new study led by researchers at The Ottawa Hospital (TOH) and the University of Ottawa suggests that a combination of two immunotherapies (oncolytic viruses and checkpoint inhibitors) could be much more successful in treating breast cancer and possibly other cancers. The study, by members of Dr. John Bell's lab in Ottawa, was funded by TFRI and other Canadian research partners and appears in Science Translational Medicine.
“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,” said Dr. Marie-Claude Bourgeois-Daigneault, lead author of the study and a postdoctoral fellow. The work was conducted in mouse models. “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,” she said in a TOH press release dated Jan 3.
In the current study, the researchers focused on “triple negative” breast cancer, which is the most aggressive and difficult-to-treat kind of breast cancer.The researchers studied three mouse models of triple-negative breast cancer, and found that all were resistant to a checkpoint inhibitor which is commonly used to treat other kinds of cancer. They also found that while an oncolytic virus called Maraba could replicate inside these cancers and help the mouse’s immune system recognize and attack the cancer, the virus alone had minimal impact on overall survival.
The researchers then tested the virus and checkpoint inhibitor together in models that mimic the metastatic spread of breast cancer after surgery, which is very common in patients. They found that this combination cured 60 to 90 per cent of the mice, compared to zero for the checkpoint inhibitor alone and 20 to 30 per cent for the virus alone. In these models, the virus was given before the surgery and the checkpoint inhibitor was given after.
“Our immune system is constantly trying to recognize and kill cancer cells, but the cancer cells are always trying to hide from it,” explained Dr. Bell, a senior scientist and project leader of TFRI's Program Project Grant on the Canadian Oncolytic Virus Consortium. “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.”
A recently published clinical trial confirmed that oncolytic viruses and checkpoint inhibitors have potential for treating melanoma, but this is the first study to show the potential in breast cancer. It is also the first study to test viruses and checkpoint inhibitors in a surgery and metastasis model, which is particularly relevant for patients.
Ongoing clinical trials are testing oncolytic viruses (including Maraba) in combination with checkpoint inhibitors in people with cancer.
The Maraba virus therapy was jointly pioneered by Dr. John Bell (The Ottawa Hospital, University of Ottawa), Dr. David Stojdl (Children’s Hospital of Eastern Ontario, University of Ottawa) and Dr. Brian Lichty (McMaster University), all members of the long-funded COVCo team.
The research described here was published in Science Translational Medicine on January 3, 2018. The publication is titled “Neo-Adjuvant Oncolytic Virotherapy Before Surgery Sensitizes Triple-Negative Breast Cancer to Immune Checkpoint Therapy”.