An armed variant of the Vaccinia oncolytic virus has demonstrated ‘great promise’ as a treatment for pancreatic cancer during preclinical investigations carried out by a team at Barts Cancer Institute (London, UK). The results of their Pancreatic Cancer Research Fund-funded investigation appeared recently in Clinical Cancer Research.
The team combined the Vaccinia virus, which can selectively target cancer cells, with a gene that is able to modulate the immune system – combining both virotherapy and immunotherapy in order to establish whether the efficacy of Vaccinia could be improved.
Oncolytic viruses have performed well in the laboratory and many studies demonstrate that they hold the ability to both destroy cancer calls and promote immunity against further cancer growth. However, such therapies have not performed well in clinical trials, as they are attacked by the immune system before they can take effect.
In an attempt to engineer the virus so that it can persist for longer, the team at Barts equipped Vaccinia with a copy of the IL-10 gene that would undergo expression once the virus infects cancer cells.
“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,” commented study lead Yaohe Wang.
After using cell lines to confirm that the addition of IL-10 did not disrupt Vaccinia’s anticancer effects, the team conducted tests comparing the effectiveness of Vaccinia with IL-10-armed Vaccinia in mice with pancreatic cancer and in a group of transgenic mice bred to develop a more human form of the disease.
After 6 weeks of treatment, 87.5% of all the mice treated with the Vaccinia–IL-10 combination were free from tumors, compared with 42.8% in those treated with Vaccinia alone. Furthermore, in the transgenic mice, the average survival rate almost doubled from 69.7 days to 138.5 days with the combination.
After being clear of any detectable primary tumors for 4 weeks, pancreatic cancer cells were then reintroduced to the mice without any further treatment with either virus. Cancer cells grew again in both groups, yet after 32 days all but one of the animals were once again clear of cancer.
Cancer regrowth was notably slower in in the mice originally treated with IL-10-armed Vaccinia and these animals were free of cancer within 18 days. Wang suggests that this finding supports other published evidence that IL-10 exerts its own anticancer effect when delivered directly into tumor tissue.
“These are exciting results, but we still have several questions. Our results show that in mice IL-10 suppresses antiviral immunity but boosts antitumor immunity – but exactly how IL-10 makes this happen remains unclear. 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,” continued Wang.
Commenting on the potential clinical impact of this work, Maggie Blanks (Pancreatic Cancer Research Fund) said: “Much more research is needed, but these early results show there’s some potential here. 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.”