Have you ever heard of an orphan virus? The term refers to a virus that hasn't yet been associated with a disease, and CRINA doctoral student Francisca Cristi-Munoz is studying one such virus, reovirus. "This virus has been found in the intestines and in the respiratory tract, it hasn't been associated with any disease… it has the ability to exclusively infect tumor cells, but leave the normal cells undamaged. It's a natural virus (that) has this ability to kill cancer cells," said Cristi-Munoz.
When researchers first began looking at reovirus, the impact it had on cancer cells was studied in animal experiments, and it proved effective. When the virus began to be used in clinical trials with humans, however, the impact wasn't as strong. Different researchers have been trying to improve the effectiveness of the virus in various ways, such as by combining the reovirus therapy with other therapies like radiotherapy and chemotherapy.
Cristi-Munoz, however, is trying to improve the virus itself. "We're trying to generate a mutant virus that is better than the natural reovirus," she said. To do this, reovirus was incubated with mutagens, and viruses that were more efficient than the natural reovirus were selected and sequenced to see which mutations were present. These viruses had three or four mutations, so Cristi-Munoz decided to generate viruses with just one mutation, to see which are the most important. She generated multiple viruses and, after testing their oncolytic potency, has narrowed it to 6 reovirus mutants that are more effective than natural reovirus. She has also combined different mutations and found that they can have additive effects in killing cancer cells.
Cristi-Munoz is trying to find a mutated version of the virus that works effectively in vivo. She is focused on breast cancer and uses animal models to see which mutated strains are most effective. "I have found if you mutate two specific proteins in this virus, you get an increased infectivity, and increased killing of cancer cells. One part [of my research] is trying to understand why this is, what the mechanisms are behind this. The other is saying, okay, we have these mutants that are better in vitro, how do they work in vivo?" The hope is that a mutated strain with increased effectiveness in mice will translate into humans, and that the more virulent mutated strains could potentially progress to clinical trials.
There are several oncolytic viruses (viruses that primarily infect and kill cancer cells), but Cristi-Munoz was drawn to reovirus in particular because it is a natural oncolytic virus (many others have been engineered for this purpose). And, since it's already being used in clinical trials, Cristi-Munoz thought it showed promise as an option for patients if it is improved. "I think in the future it will be a good alternative [to other forms of therapy]."
Cristi-Munoz is an international student who earned a BSc and MSc in Biochemistry in Chile, before spending a few years working in the Immunology field. She moved to Edmonton with her husband, who was doing a PhD, and eventually decided to continue her studies at the doctoral level at the University of Alberta as well. She has two supervisors, Dr. Maya Shmulevitz and Dr. Mary Hitt. Cristi-Munoz received a partial stipend for this project from the Cancer Research Institute of Northern Alberta (CRINA) thanks to the Roses of Hope Foundation, a charitable organization backed by La Vie en Rose and its clients in support of women's health.