A collaborate effort between Peter A. Forsyth M.D.of Moffitts’ Neuro-Oncology Program, Tampa, Florida, University of Calgary, University of Texas, University of Florida and Ottawa Regional Cancer Centre Research Laboratories have found that a combination of the myxoma virus (an oncolytic virus) and the immune suppressant rapamycin (an antibiotic) has the ability to kill glioblastoma multiforme. Glioblastoma multiforme happens to be the most common and most aggressive malignant brain tumor in humans that involves glial cells. According to Forsyth, the combination of this virus and antibiotic can infect and kill brain cancer stem cells as well as differentiated compartments of glioblastoma multiforme.
Temozolomide is often used to treat glioblastoma multiforme, however, the tumor is resistant to this drug. Forsyth points out, “Oncolytic viruses that infect and break down cancer cells offer promising possibilities for overcoming resistance to targeted therapies. Based on our previous work with myxoma virus, we considered it to be an excellent oncolytic virus candidate against brain cancer stem cells.”
These researchers believe that oncolytic viruses have the ability to attack the tumor in several ways. They have the ability to kill cancer cells directly by simply infecting them. On the other hand, they appear to be able to induce the immune system to attack the tumor. This suggests this type of therapy can bypass the classical resistance mechanisms that have plagued current therapies.
To date, brain cancer stem cells have been found to be susceptible to myxoma virus in cell cultures and in animal models, including cells lines that are temozolomide resistant. “We also found that myxoma virus with rapamycin is a potentially useful combination. The idea that cancer cells can be killed by a harmless virus is an exciting prospect for therapy,” Forsyth said.
The combination of this oncolytic virus and antibiotic is not a cure at the moment but rather a step forward. How rapamycin works to enhance infection of brain stem cells is unknown, but researchers are searching for other drugs that may increase the effectiveness of the myxoma virus. They are also testing other strains of this virus to see if there are more potent forms.
This research establishes myxoma virus as having the ability to infect and kill glioblastoma multiforme so it will be added to the list of oncolytic viruses that kill these types of cells. This provides support for clinical application as this model will need to be tested on patients to determine safety. According to these researchers, “We expect that intracranial injections of myxoma virus will be safe based on our extensive preclinical work and the demonstrated safety of other oncolytic viruses in clinical trials.”