Jun 13, 2012 6:37pm
Common Cold Virus Attacks Cancer, Study Finds
A virus that causes the common cold can also track and attack tumors, according to a new study that opens the door to novel cancer treatments.
British researchers injected reovirus into the bloodstreams of 10 patients with bowel cancer that had spread to the liver and found the virus set up deadly “reproduction factories” in the tumors but not in healthy tissue.
“It seems that reovirus is even cleverer than we had thought,” study author Dr. Alan Melcher, professor of clinical oncology and biotherapy at Leeds University in the U.K. said in a statement. “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.”
The findings, published today in the journal Science Translational Medicine, suggest cancer-killing viruses can target hard-to-treat tumors after being injected into the bloodstream like standard chemotherapies.
“It would have been a significant barrier to their widespread use if they could only have been injected into the tumor, but the finding that they can hitch a ride on blood cells will potentially make them relevant to a broad range of cancers,” study co-author Dr. Kevin Harrington of the Institute of Cancer Research said in a statement. “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.”
Other viral cancer therapies, some of which require direct injection into tumors, are currently in phase 3 testing. But this is the first time reovirus has been shown to safely and effectively home in on tumors through the blood.
In an accompanying editorial, John Bell of the Ottawa Hospital Research Institute in Canada said the study provides an “important proof-of-concept” for intravenous viral cancer therapies.
“The authors and, more importantly, the patients who participated in this trial have made crucial contributions to the translation of [oncolytic virus]-based therapies,” he wrote.
13 June 2012 Last updated at 18:01 GMT
'Hitchhiking' anti-cancer viruses ride blood cells
By James Gallagher
Health and science reporter, BBC News
A tumour-killing virus can sneak around the body by "hitchhiking" on the back of blood cells, researchers have shown.
It is hoped reoviruses can be used to treat cancer, but there were fears they would not work if the immune system could wipe them out.
A study published in Science Translational Medicine showed the viruses could hide in the blood and reach their target.
Experts said it was an important step in advancing cancer therapies.
Reoviruses are normally harmless, but they can cause stomach upsets and colds in childhood. However, it seems they have the ability to infect and kill some cancerous cells while leaving the surrounding tissue unharmed.
However, experiments on mice suggested the virus would not survive in the blood as the immune system would destroy it.
It meant the virus would need to be injected directly into the tumour or be given with drugs to suppress the immune system.
A study in 10 people at the University of Leeds and The Institute of Cancer Research, at the Royal Marsden Hospital, showed that the virus could escape the immune system by hiding in the blood.
Continue reading the main story
Viral treatments like reovirus are showing real promise in patient trials”
Dr Kevin Harrington
The Institute of Cancer Research
All the patients had advanced bowel cancer which had spread to the liver, and were injected with doses of the reovirus ahead of their scheduled surgery.
The virus was detected in the tumour, but not the liver, meaning it was selectively targeting the cancer. In the blood, the virus was detected in blood cells, not the liquid blood plasma all the cells float in, meaning it was "hitchhiking", the researchers said.
Prof Alan Melcher, from the University of Leeds, said the virus was "even cleverer" than previously thought.
"By piggybacking on blood cells, the virus is managing to hide from the body's natural immune response and reach its target intact."
He told the BBC he had "no doubt" the virus would be eventually used "in combination with chemotherapy".
'Important next step'
Dr Kevin Harrington, from the Institute of Cancer Research, said: "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."
Why reoviruses affect only cancer cells is not entirely understood. Cancer cells behave very differently to healthy cells, which may make them more susceptible to infection.
Doctors are already testing the virus in some trials in people, such as studies on head and neck cancer.
Prof John Bell, from the University of Ottawa, has researched using genetically modified viruses to attack cancer cells.
He said viruses could be "exquisitely selective" in targeting tumours, and that this latest study had shown how safe the technique was.
"This study is an important next step in advancing oncolytic virus therapies into cancer patients."
Sci Transl Med 13 June 2012:
Vol. 4, Issue 138, p. 138ra77
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003578
Cell Carriage, Delivery, and Selective Replication of an Oncolytic Virus in Tumor in Patients
Robert A. Adair1,*, Victoria Roulstone2,*, Karen J. Scott1, Ruth Morgan1, Gerard J. Nuovo3, Martin Fuller4, Deborah Beirne1, Emma J. West1, Victoria A. Jennings1, Ailsa Rose1, Joan Kyula2, Sheila Fraser1, Rajiv Dave1, David A. Anthoney1, Alison Merrick1, Robin Prestwich1, Amer Aldouri1, Oliver Donnelly1, Hardev Pandha5, Matt Coffey6, Peter Selby1, Richard Vile7, Giles Toogood1, Kevin Harrington2,* and Alan A. Melcher1,*,†
+ Author Affiliations
1Leeds Institute of Molecular Medicine, St. James’s University Hospital, Leeds LS9 7TF, UK.
2Institute of Cancer Research, Centre for Cell and Molecular Biology, Chester Beatty Laboratories, London SW3 6JB, UK.
3Comprehensive Cancer Centre, Ohio State University, Columbus, OH 43210, USA.
4Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
5Postgraduate Medical School, University of Surrey, Guildford GU2 7WG, UK.
6Oncolytics Biotech Inc., Calgary, Alberta T2N 1X7, Canada.
7Molecular Medicine Program and Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: firstname.lastname@example.org
Oncolytic viruses, which preferentially lyse cancer cells and stimulate an antitumor immune response, represent a promising approach to the treatment of cancer. However, how they evade the antiviral immune response and their selective delivery to, and replication in, tumor over normal tissue has not been investigated in humans. Here, we treated patients with a single cycle of intravenous reovirus before planned surgery to resect colorectal cancer metastases in the liver. Tracking the viral genome in the circulation showed that reovirus could be detected in plasma and blood mononuclear, granulocyte, and platelet cell compartments after infusion. Despite the presence of neutralizing antibodies before viral infusion in all patients, replication-competent reovirus that retained cytotoxicity was recovered from blood cells but not plasma, suggesting that transport by cells could protect virus for potential delivery to tumors. Analysis of surgical specimens demonstrated greater, preferential expression of reovirus protein in malignant cells compared to either tumor stroma or surrounding normal liver tissue. There was evidence of viral factories within tumor, and recovery of replicating virus from tumor (but not normal liver) was achieved in all four patients from whom fresh tissue was available. Hence, reovirus could be protected from neutralizing antibodies after systemic administration by immune cell carriage, which delivered reovirus to tumor. These findings suggest new preclinical and clinical scheduling and treatment combination strategies to enhance in vivo immune evasion and effective intravenous delivery of oncolytic viruses to patients in vivo.
Copyright c 2012, American Association for the Advancement of Science
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