Viruses and Checkpoint Inhibitors Combine to Form an Effective Cancer Treatment

Researchers here demonstrate a combination therapy that is far more effective in destroying a target cancer than either of its components alone. Effective synergies between therapies are discovered at a fairly low rate by the scientific community, which is in part a reflection of their rarity, but also a reflection of the fact that the regulatory system is not set up to encourage the commercial development of combination therapies. The number of trials for such efforts is small in comparison to single therapy tests. There isn't a good response to this observation beyond the usual calls for more freedom and more funding.

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 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. "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 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 percent of the mice, compared to zero for the checkpoint inhibitor alone and 20 to 30 percent for the virus alone. In these models, the virus was given before the surgery and the checkpoint inhibitor was given after. "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." Ongoing clinical trials are testing oncolytic viruses (including Maraba) in combination with checkpoint inhibitors in people with cancer.

Link: http://www.ohri.ca/newsroom/newsstory.asp?ID=1000

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