Researchers from the University of Alberta have been learning how to use viruses to slow the growth of cancer.
The team, led by then-PhD candidate Chad Irwin, studied the cancer-fighting properties of myxoma virus, a type of poxvirus, which was initially used to control rabbit populations in Australia, said Dr. David Evans.
“The [virus] is totally harmless in humans, but then Chad said it was discovered that it has the capacity to infect and kill transformed cells, and that’s because during the course of their development mutations occur, which make them cancerous, and make them resistant to the immune system,” said Evans. “It’s kind of like you have a choice: you become a cancer cell and be sensitive to virus, or resistant to virus and not be a cancer cell.”
The researchers compared the virus to vaccinia virus, which was originally used by the World Health Organization (WHO) to eradicate small pox. Vaccinia spreads efficiently throughout human cells, said Irwin.
According to Evans, the other issue with myxoma was that it has difficulties exiting the cell after completing the assembly of the new viruses.
“So we knew that vaccinia spread very, very well and that myxoma spreads quite poorly. So what we tried to figure out is, ‘What’s different between these viruses in terms of their spread?’ And it led us to this one gene, called f11, which basically its role is to mess with actin and that helps it get out. When we went looking for genes between these two viruses, it turns out myxoma doesn’t have that,” Irwin said.
The team spliced the f11 gene into myxoma virus to test its ability to spread and reduce human breast cancer tumor growth in immuno-compromised mice.
Not only did the team find that the tumor growth was reduced, they also found that the virus was able to spread to cancers that have metastasized and began to grow in other regions of the body, said Irwin.
“We saw that not only did it do a better job in the site where we introduced it, but it could also spread better throughout the mouse and go to a second tumor and do a better job at controlling the tumor growth, because that’s really one of the major problems with cancer is not necessarily the primary tumor that you find, but where it metastasizes and goes to other places such as the lungs, or the heart or other organs like the brain,” Irwin said. “So if you can get a virus that not only goes after that but goes systemically and goes after those metastases then it’s a better virus potentially.”
That being said, the virus did not completely eradicate the cancer, but would only slow its growth.
“With this one, we weren’t able to completely eradicate the tumors. They still grow — it just slows them down. There is probably still work that needs to be done to make it more effective,” Irwin said. “Myxoma looks like it will be very effective treating blood cancer, so you can take out bone marrow and treat it with myxoma and put it back into someone and it looks like it works very well with that.”
The researchers are not planning to continue doing trials with myxoma, but instead will be focusing on vaccinia virus for clinical trials that are scheduled to take place in the summer, Irwin said.
According to Evans, the field of oncolytics is undergoing a bit of resurgence, although the field has been around since the late 1800s, when doctors found that they could cure a small number of patients with severe cancers by injecting them with Coley’s toxin, tetanus and a number of other strong vaccines.
“It’s still debated whether it is real or not, and doctors argue back and forth. It was never done in a controlled manner because this all predates clinical trials — it was just doctors trying things, which they could do in those days,” Evans said. “And what was probably going on was these very powerful vaccines turning on an immune response to the vaccine and, in the course of doing that, reactivating an incipient response to a tumor antigen. And the tumors that responded were often the ones that are known to be sensitive to immune surveillance, such as melanomas.”
“There is a literature that says we can do this, and there is a huge other field of treating cancer by immune strategies.”