Glioblastoma brain tumors are relentless, hard-to-treat, and often lethal. The five-year survival rate ranges from 6 percent (for ages 55-64) to 22% (for ages 20-44). Yale Cancer Center scientists have enlisted a most unlikely ally in efforts to treat this form of cancer—elements of the Ebola virus.
“The irony is that one of the world’s deadliest viruses may be useful in treating one of the deadliest of brain cancers,” said Yale Cancer Center’s Anthony van den Pol, professor of neurosurgery, who passed away on October 28, 2020. Prior to his death, he described the Yale efforts in the Journal of Virology.
The approach takes advantage of a weakness in most cancer tumors, as well as an Ebola defense against the immune system response to pathogens.
Unlike normal cells, a large percentage of cancer cells lack the ability to generate an innate immune response against invaders such as viruses. This has led cancer researchers to explore the use of viruses to combat a variety of cancers.
Using viruses carries an obvious risk—they can introduce potentially dangerous infections. The Ebola virus itself has had a lethality of nearly 90 percent during outbreaks.
To get around this problem, scientists, including van den Pol, have experimented with creating or testing chimeric viruses, or a combination of genes from multiple viruses. They have the ability to target cancer cells without harming patients.
One of the seven genes of the Ebola virus that helps it avoid an immune system response also contributes to its lethality. This intrigued van den Pol.
He and the study’s first author, Xue Zhang, formerly of Yale, used a chimeric virus containing one gene from the Ebola virus—a glycoprotein with a mucin-like domain (MLD).
Glycoproteins play a large role in many biological processes and diseases. In wild-type Ebola virus, the MLD, which is contained in a subunit of the Ebola virus’ glycoprotein, is one of the reasons why the virus is so lethal. But it also plays a role in hiding Ebola from the immune system.
They injected this chimeric virus with and without the MLD into the brains of mice with glioblastoma and found that the MLD helped selectively target and kill deadly glioblastoma brain tumors. MLD increased the survival rate to 50 percent compared to 19 percent when the MLD was not present. In addition, the MLD was substantially safer.
Van den Pol said the MLD’s beneficial effect appears to be that it protects normal cells from infection—but not cancer cells, which lack the ability to mount an immune response to pathogens.
A key factor may be that the virus with the glycoprotein MLD replicates less rapidly, potentially making it safer than viruses without the MLD part of the glycoprotein, he said.
In theory, such a virus might be used in conjunction with surgery to eliminate glioblastoma tumors and help prevent a recurrence of cancer, Van den Pol said.
The research was funded by the National Cancer Institute of the National Institutes of Health.
Originally published Feb. 12, 2020; updated May 16, 2022.