Intravenous Delivery of Oncolytic Reovirus Primes Tumours for Better Cancer Strategy Response
Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies.
But the catch is that they do not treat all cancers, and neither breast nor brain tumors are usually treatable with these drugs.
Now, in two sets of completely independent studies, scientists have shown 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.
In a study at the University of Leeds in the U.K, scientists demonstrate how intravenous oncolytic human Orthoreovirus (reovirus) therapy administered prior to surgery to remove tumors elucidated positive data from an early clinical trial in nine patients with either glioma or brain metastases.
The findings showed that the intravenously delivered virus could cross the blood-brain barrier and infect tumors, and there was evidence that the virus also stimulated the immune system to target the tumor. The findings have led to the start of a clinical trial in which patients are receiving reovirus in combination with radiotherapy and chemotherapy following surgery.
“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 that this type of immunotherapy could be used to treat more people with aggressive brain cancers,
” said Adel Samson, a medical oncologist at the Leeds Institute of Cancer and Pathology. “This study was about showing that a virus could be delivered to a tumour in the brain. Not only was it able to reach its target, but there were signs it stimulated the body’s own immune defences to attack the cancer.”In another study by researchers at the University of Ottawa and Ottawa Hospital, it was 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 combination 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.
Ongoing clinical trials are testing oncolytic viruses (including Maraba) in combination with checkpoint inhibitors in people with cancer. People who are interested in these trials at The Ottawa Hospital can read these frequently asked questions.
“ACGT has long believed that the cure for cancer lies in the genes,” said Margaret Cianci, executive director of the Alliance for Cancer Gene Therapy. “Using tools like viruses and checkpoint inhibitors to activate the immune system and create a cellular response against cancer is incredibly promising. We always have big hopes for our scientific grants and to see results like these is very exciting.“