Scientists have discovered when a cancer-killing virus is injected in
the bloodstream it hitches a ride on blood cells and evades attack from
the
immune system, allowing it to reach cancer tumors, and start destroying
cancer cells. They suggest this means it may be possible to use promising "viral
therapy" during routine outpatient sessions, like chemotherapy, to treat a wide range of cancers.
Certain viruses, like the reovirus, that causes colds and mild stomach upsets, prefer to attack cancer cells. They also stimulate the immune system to attack tumors.
Using these "oncolytic" viruses to kill cancer is a fairly new approach that is currently being tested. Trials are currently under way to test "viral therapy" as an approach to treat cancer in human patients.
But the challenge is how to get the viruses into tumors without alerting the immune system to destroy them. One way is to inject them into the tumors, but this is technically difficult and particularly so for tumors that are deep inside the body, such as in the lungs, stomach, liver and pancreas.
Another way could be to inject the virus into the bloodstream; however, scientists have assumed this would not be feasible because the virus would likely be spotted and destroyed by the immune system before it could reach the tumor.
But when a group of scientists decided to test this by injecting the virus into the bloodstream of patients with advanced colorectal cancer, they found the virus was able to evade the immune system by "going under cover" and hitching a ride on red blood cells.
The study, led by researchers from the University of Leeds and The Institute of Cancer Research (ICR) in the UK, reveals how the "hitch-hiking" virus is shielded from antibodies in the bloodstream that might otherwise neutralize its anti-cancer properties.
The team writes about its work in a paper published online in Science Translational Medicine on 13 June.
The study participants were 10 patients with advanced colorectal cancer that had spread to the liver and who were scheduled to undergo surgery on the secondary tumors in their livers.
In the weeks leading up to their surgery, all patients received up to five doses of the reovirus as outpatients.
From blood samples taken shortly after treatment, the researchers found that the active virus associated with blood cells. Later samples showed the virus was no longer in the blood cells and had quickly cleared from the system.
When the researchers examined samples of liver tissue removed during surgery up to four weeks later, they found "viral factories" and active virus in the tumor samples but not in normal tissue samples. This confirmed the virus had travelled specifically to the tumor after being injected into the bloodstream.
Professor Alan Melcher of the University of Leeds, and Dr Kevin Harrington from The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, jointly led the study.
Melcher told the press:
"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. This could be hugely significant for the uptake of viral therapies like this in clinical practice."
Harrington commented that:
"Viral treatments like reovirus are showing real 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," he added.
He said if these treatments could only be delivered by injecting into the tumor, they would have limited use, but discovering that the virus "can hitch a ride on blood cells will potentially make them relevant to a broad range of cancers".
"We also confirmed that reovirus was specifically targeting cancer cells and leaving normal cells alone, which we hope should mean fewer side-effects for patients," said Harrington.
Funds from Cancer Research UK, Leeds Experimental Cancer Medicine Centre, University of Leeds, The Institute of Cancer Research, Leeds Cancer Vaccine Appeal, and the Rays of Hope Appeal, paid for the study.
Certain viruses, like the reovirus, that causes colds and mild stomach upsets, prefer to attack cancer cells. They also stimulate the immune system to attack tumors.
Using these "oncolytic" viruses to kill cancer is a fairly new approach that is currently being tested. Trials are currently under way to test "viral therapy" as an approach to treat cancer in human patients.
But the challenge is how to get the viruses into tumors without alerting the immune system to destroy them. One way is to inject them into the tumors, but this is technically difficult and particularly so for tumors that are deep inside the body, such as in the lungs, stomach, liver and pancreas.
Another way could be to inject the virus into the bloodstream; however, scientists have assumed this would not be feasible because the virus would likely be spotted and destroyed by the immune system before it could reach the tumor.
But when a group of scientists decided to test this by injecting the virus into the bloodstream of patients with advanced colorectal cancer, they found the virus was able to evade the immune system by "going under cover" and hitching a ride on red blood cells.
The study, led by researchers from the University of Leeds and The Institute of Cancer Research (ICR) in the UK, reveals how the "hitch-hiking" virus is shielded from antibodies in the bloodstream that might otherwise neutralize its anti-cancer properties.
The team writes about its work in a paper published online in Science Translational Medicine on 13 June.
The study participants were 10 patients with advanced colorectal cancer that had spread to the liver and who were scheduled to undergo surgery on the secondary tumors in their livers.
In the weeks leading up to their surgery, all patients received up to five doses of the reovirus as outpatients.
From blood samples taken shortly after treatment, the researchers found that the active virus associated with blood cells. Later samples showed the virus was no longer in the blood cells and had quickly cleared from the system.
When the researchers examined samples of liver tissue removed during surgery up to four weeks later, they found "viral factories" and active virus in the tumor samples but not in normal tissue samples. This confirmed the virus had travelled specifically to the tumor after being injected into the bloodstream.
Professor Alan Melcher of the University of Leeds, and Dr Kevin Harrington from The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, jointly led the study.
Melcher told the press:
"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. This could be hugely significant for the uptake of viral therapies like this in clinical practice."
Harrington commented that:
"Viral treatments like reovirus are showing real 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," he added.
He said if these treatments could only be delivered by injecting into the tumor, they would have limited use, but discovering that the virus "can hitch a ride on blood cells will potentially make them relevant to a broad range of cancers".
"We also confirmed that reovirus was specifically targeting cancer cells and leaving normal cells alone, which we hope should mean fewer side-effects for patients," said Harrington.
Funds from Cancer Research UK, Leeds Experimental Cancer Medicine Centre, University of Leeds, The Institute of Cancer Research, Leeds Cancer Vaccine Appeal, and the Rays of Hope Appeal, paid for the study.
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