Researchers have shown that a cold virus known to destroy cancer cells can be delivered to a tumour through the bloodstream without falling prey to killer antibodies on the way.
In a study published Wednesday in the journal Science Translational Medicine, the researchers found the “reovirus” hitches a ride on blood cells and uses them as a shield against the immune-system cells.
The reovirus holds promise as a possible new way of treating cancer because it not only kills cancer cells directly, but also triggers an immune response — similar to what a vaccine does — that helps eliminate residual cancer cells.
But because the virus, which causes upper respiratory and gastrointestinal illness, is common in the environment, most people have been exposed to it in childhood and therefore have developed antibodies, said Alan Melcher, a professor of clinical oncology and biotherapy at the University of Leeds who co-led the study.
“What people thought that meant was that if you’ve got antibodies against the virus, if you just inject it into the bloodstream, it can never work because it will just be neutralized by the antibodies,” Melcher said Wednesday from Leeds, England.
“But what we were able to show, actually, was that by associating with blood cells in the blood, the virus can effectively hide from the antibodies and therefore get transported through the circulation and so get to the tumour.”
The study involved 10 patients with advanced colorectal cancer who were due to have surgery on tumours that had spread to the liver. All patients were given up to five intravenous doses of the reovirus in the weeks before their operations.
Blood tests carried out shortly after treatment found the active virus tagging along with blood cells, but later tests showed the virus was quickly cleared from the bloodstream.
However, when researchers looked at the malignant liver tissue removed during surgery up to four weeks later, they found “viral factories” and active virus in the tumour — but not in normal liver tissue.
“It seems that reovirus is even cleverer than we had thought. By piggybacking on blood cells, the virus is managing to hide from the body’s natural immune response and reach its target intact,” Melcher said. “This could be hugely significant for the uptake of viral therapies like this in clinical practice.”
The study was not intended to see if the reovirus can shrink or eliminate tumours — that question is being explored in much larger trials of patients with a variety of cancers — but it does provide proof-of-concept that intravenously delivered reovirus-based cancer therapy is possible, he said.
Doctors haven’t been sure what’s the best way to deliver experimental virus-based treatments. Viruses with cancer-killing properties can be injected directly into tumours, but the procedure is invasive and complicated, especially with tumours deep within the body, such as the liver, lungs and pancreas.
Dr. Kevin Harrington of the Institute of Cancer Research, who jointly led the study, said viral treatments like reovirus are showing great promise in patient trials.
“This study gives us the very good news that it should be possible to deliver these treatments with a simple injection into the bloodstream,” Harrington said.
“It would have been a significant barrier to their widespread use if they could only have been injected into the tumour.
“But the finding that they can hitch a ride on blood cells will potentially make them relevant to a broad range of cancers.”
The reovirus used, called Reolysin, is produced by Calgary-based Oncolytics Biotech Inc. The company is also involved in several clinical trials, including one to assess the viral treatment in patients with head and neck cancers.
John Bell, a senior scientist in cancer therapeutics at the Ottawa Hospital Research Institute, described the U.K. study as an “elegant clinical trial” and “really important work that can advance the field.”
Bell, who has been working with another anti-cancer virus known as JX-594, believes viral therapy could offer another potent tool for doctors treating various kinds of malignancies.
“This is undoubtedly, if these trials hold up, a completely different way of treating the disease.”
Melcher said the beauty of an agent like the reovirus is that patients suffer little or no adverse effects — at the worst they have mild and short-lived flu-like symptoms.
“So the side-effects are very different compared to something like chemotherapy or radiotherapy,” he said. “And it means that these viruses can be used in combination with other things like chemotherapy, and I’m sure that’s going to be the way forward.
“They’re not going to replace current cancer treatments, they’re going to be additions to it, we hope.”