The potential of virotherapy – using oncolytic viruses to treat cancer – is proving difficult to realize. Although lab studies show oncolytic viruses kill cancer cells, leave normal cells intact and prevent cancer regrowth, results from clinical trials have been disappointing – the immune system tends to defeat the virus before it can take effect. Now new research shows adding immunotherapy to virotherapy may make it more effective.
The researchers – led by Queen Mary University of London (QMUL) in the UK – report their findings in the journal Clinical Cancer Research.
They describe how arming the oncolytic virus Vaccinia with a gene that influences the body’s immune system so it does not attack the virus before it can get to work, may be an effective treatment for pancreatic cancer.
The team armed the Vaccinia virus with a copy of the interleukin-10 (IL-10) gene, which expresses proteins important in cell signaling that are also known to dampen immune response.
Study leader Dr. Yaohe Wang, of the Centre for Molecular Oncology at QMUL’s Barts Cancer Institute, explains why they focused on this particular gene:
“Many viruses use IL-10 to hide from the host’s immune system, so we thought we’d use this natural strategy to investigate whether it would improve Vaccinia’s effectiveness.”
To begin with, Dr. Wang and colleagues worked with cell lines. They showed arming Vaccinia with the IL-10 gene did not diminish the cancer-fighting properties of the oncolytic virus.
They then moved onto mice. They compared the effect of Vaccinia with and without IL-10 on mice with pancreatic cancer (the subcutaneous group), and also on another group of mice genetically engineered to develop a more human form of the disease (the transgenic group).
The results showed that 6 weeks after treatment, 87.5% of all the mice receiving the combination of Vaccinia with IL-10 were completely free of tumors compared with only 42.8% of those treated with Vaccinia alone.
Also, in the transgenic mice, the survival rate of those receiving Vaccinia armed with IL-10 was almost twice that of mice that received Vaccinia alone (138.5 days compared with 69.7 days).
The researchers also tested what happened when, 4 weeks after the mice were completely clear of primary pancreatic cancer tumors, they reintroduced pancreatic cancer cells into the animals and gave them no further treatment.
They found that while cancer cells grew again in both the Vaccinia armed with IL-10 and the Vaccinia alone mice, all the mice except for one were completely clear of cancer after 32 days. However, the regrowth was slower in the Vaccinia armed with IL-10 mice – and they were free of cancer after only 18 days.
Dr. Wang says their findings concur with other recently published studies that have raised the idea that IL-10 may have its own anti-cancer effect when delivered directly into tumors.
He explains that while their results are “exciting” there are still several questions to answer. For example, their results indicate that IL-10 stops the immune system from attacking the virus, but helps it fight cancer. They need to understand how it does this.
“This is something we’re already investigating as understanding this mechanism will provide a foundation for designing clinical trials to treat pancreatic cancer with this IL-10 armed virus,” notes Dr. Wang.
The study was funded by the UK charity Pancreatic Cancer Research Fund. Their CEO – Maggie Blanks – says while more research is needed, these early results look promising, and notes:
“Pancreatic cancer desperately needs a radical new approach to see improvement in survival, so a new treatment that also offers protection against disease recurrence would be an extremely important development.”
Pancreatic cancer is a notoriously difficult cancer to spot in the early stages. Currently, only around 6% of patients live more than 5 years after diagnosis – with most cases only being diagnosed after the cancer has started to spread.
In November 2014, Medical News Today learned of another study where researchers identified the first molecular steps that lead to pancreatic cancer. In the journal Cancer Discovery, the team reports how they found the starting point when certain cells in the pancreas become pre-cancerous lesions. They believe their finding opens the door to exploring ways to prevent the deadly disease.