‘Hitchhiking’ Viral Therapy Deals a Double Blow to Cancer

Newswise — Scientists have shown how a promising viral therapy that delivers a double blow to cancer can sneak up on tumors undetected by hitching a ride on blood cells.

The work, led by researchers from the University of Leeds and The Institute of Cancer Research (ICR), reveals how the ‘hitchhiking’ virus is shielded from antibodies in the blood stream that might otherwise neutralize its anti-cancer properties.

The findings, from a study in patients, suggest that viral therapies like this can be effectively injected into the bloodstream during routine outpatient appointments - just like standard chemotherapy agents – making them potentially suitable for use against a wide range of cancers.

Reovirus is a promising new way of treating cancer that attacks the disease on two fronts. Not only does the virus kill cancer cells directly, but it also triggers an immune response - like a vaccine – that helps eliminate residual cancer cells.

Many patient trials of reovirus are currently underway, including several in the UK led by the same University of Leeds and ICR scientists. Up until now, however, doctors have not been sure about the best way to deliver the experimental treatment. Although the virus can be injected directly into tumors, this is a relatively complicated procedure requiring considerable technical expertise. This delivery method also makes it difficult to treat tumors deep within the body, such as the liver, lungs, pancreas, and stomach.

Researchers had been concerned that reovirus might not reach the tumors it was supposed to treat if it was delivered intravenously, like standard chemotherapy agents are. They had expected that antibodies in the blood would mop up and neutralize the virus before it arrived at its intended target.

But now tests on a small group of patients have shown that this is not the case. In fact, not only did the virus stay active during its journey through the bloodstream but it also homed in on cancer cells, ignoring nearby healthy tissue.

University of Leeds’ researcher Professor Alan Melcher, who receives funding from Cancer Research UK, jointly led the study. He said: “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.”

Dr Kevin Harrington from The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, who jointly led the study, 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. 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. 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.”

The study involved 10 patients with advanced bowel cancer who were due to have surgery on tumors that had spread to the liver. All patients were given up to five doses of the reovirus in the weeks before surgery as outpatients.

Blood tests carried out shortly after treatment found the active virus associated with blood cells. Samples taken later showed that the hitch-hiking virus did not overstay its welcome with the cells and was cleared quickly from the system.

When researchers looked at pieces of tissue removed during surgery up to four weeks later, they found ‘viral factories’ and active virus in the tumor, but not normal liver. This confirmed that the reovirus had been delivered specifically to the cancer after being injected into the bloodstream.

Dr Julie Sharp, senior science information manager at Cancer Research UK, which part-funded the research, said: “This promising study shows that reovirus can trick the body’s defenses to reach and kill cancer cells and suggests that it could be given to patients using a simple injection. We look forward to seeing how this research develops and if this could one day become part of standard cancer treatment.”

Full details of the work are published today in the journal Science Translational Medicine. The paper covers findings from the U.K. translational clinical trial (REO 013) investigating intravenous administration of REOLYSIN (Oncolytics Biotech) in patients with metastatic colorectal cancer prior to surgical resection of liver metastases.

The work was funded by 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.

Further information:

Professor Alan Melcher is available for interview.

Notes for Editors

1. The paper: Adair, RA, "Cell Carriage, Delivery, and Selective Replication of an Onocolytic Virus in Tumor in Patients," is available to journalists at http://www.eurekalert.org/jrnls/scitransmed/. Alternatively, please contact the Science press office on +1 202-326-6440 or [email protected].

2. One of the UK’s largest medical, health and bioscience research bases, the University of Leeds delivers world leading research in medical engineering, cancer, cardiovascular studies, epidemiology, molecular genetics, musculoskeletal medicine, dentistry, psychology and applied health. Treatments and initiatives developed in Leeds are transforming the lives of people worldwide with conditions such as diabetes, HIV, tuberculosis and malaria. www.leeds.ac.uk

3. The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes. Scientists and clinicians at the ICR are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally. www.icr.ac.uk and www.royalmarsden.nhs.uk

The Royal Marsden NHS Foundation TrustThe Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education. Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex. www.royalmarsden.nhs.uk

4. Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research. The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years. Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1861 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook

5. Oncolytics Biotech Inc.Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics’ clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com

Professor Alan Melcher is available for interview.