A pair of studies show that tumor-targeting viruses can rally the immune system against breast and brain cancers, boosting the efficacy of immunotherapy drugs and opening the door to promising combination treatments for aggressive and difficult-to-treat cancers.
Many viruses naturally target and kill cancer cells, and experimental oncolytic viruses are often engineered to improve that ability. That should them an attractive option to fight tumor cells, which the body normally identifies as “self.” But oncolytic viruses have shown limited effectiveness in human trials.
In the first study, researchers from the University of Ottawa and Ottawa Hospital found that the oncolytic virus Maraba could replicate within the tumors of mouse models of triple-negative breast cancer. The team then deployed the virus along with a checkpoint inhibitor—a drug that blocks proteins that normally prevent the immune system from recognizing and eradicating cancer. The combo worked in more than 60% of the mice after surgery, while the virus alone prevented relapse in just 20% to 30% of the animals, according to a press release. The checkpoint inhibitor alone was not effective at all.
The combo treatment works by identifying the tumor to the immune system and then unleashing a T-cell attack on the cancer.
"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,” said John Bell, a senior scientist at the Ottawa Hospital and professor at the University of Ottawa, in the release. The results appear in Science Translational Medicine.
Pairing tumor-targeting viruses and checkpoint inhibitors is not a new idea—a phase 2 trial recently demonstrated that combining Amgen’s oncolytic drug Imlygic with Bristol-Myers’ checkpoint inhibitor Yervoy doubled patients’ response rates compared to using the latter alone.
But could such combos help cancer drugs get past the blood-brain barrier, which has long stymied efforts to create drugs for various diseases? Scientists previously thought the only way to deliver such viruses to the brain was direct injection, which isn’t suitable for all patients and difficult to repeat. But a second study on oncolytic viruses, published in Science Translational Medicine, showed that the reovirus found its way to the brain after intravenous administration.
A U.K. team deployed reovirus—a family of viruses that primarily causes symptoms in children—in a trial with nine patients who had hard-to-reach brain tumors. They were slated for tumor-removal surgery and given a dose of the virus prior to their operation. The scientists analyzed the tumors and found the virus was able to cross the blood-brain barrier. In the brain, it called forth “killer” T cells to attack the cancer.
"This is the first time it has been shown that a therapeutic virus is able to pass through the brain-blood barrier, and that opens up the possibility this type of immunotherapy could be used to treat more people with aggressive brain cancers,” said Dr Adel Samson, co-lead author and a medical oncologist at the University of Leeds, in a statement.
While the reovirus was used alone in the study, the team is looking to investigate combination treatments and has already started a trial testing reovirus alongside radiotherapy and chemotherapy following surgery. And though the initial study used just one dose of the virus, the researchers have decided to try giving repeated doses to patients.