Researchers have discovered a way to harness the lethal abilities of the Ebola virus to target and kill glioma cells in mice models — and they think that their research, published in the Journal of Virology, could provide a rationale for the development of an Ebola-derived oncolytic therapy for brain cancer in humans.1
In a preclinical model, investigators from Yale University in New Haven, Connecticut, tested chimeric viruses made with vesicular stomatitis virus (VSV), swapping in the glycoprotein of the Ebola virus in place of the normal VSV protein in some of the recombinant versions. And in some of the chimeras, the sequence for the mucin-like domain (MLD) was present in the Ebola glycoprotein. This MLD glycoprotein, derived from the full Ebola virus, typically allows the virus to evade the immune system — a factor that contributes to the lethal nature of this RNA virus.
“The irony is that one of the world’s deadliest viruses may be useful in treating one of the deadliest of brain cancers,” lead study researcher Anthony van den Pol, PhD, professor of neurology at Yale University, said in an institutional press release.2
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The MLD section of Ebola is thought to act like a “glycosylated umbrella shielding the viral [glycoprotein] from neutralization by the adaptive immune response,” according to study authors.1
Once injected into the human glioma tumors of xenotransplant immunodeficient mice, the chimeric VSVs that lacked the MLD section of the Ebola virus propagated more quickly compared with the full-length Ebola VSV chimera that had MLD.
Compared with controls, tumor mass was less pronounced in Ebola virus-treated mouse brains. And, the group of mice that was treated with the MLD-retaining chimeric virus had prolonged survival compared with the mice in the groups treated with other versions of the virus. In fact, the chimera lacking MLD “generated a more than 10-fold greater release of infectious viral progeny” in both human glioblastoma and mouse brain cells than the version that had the MLD glycoprotein.
Although most of the lesions shrank across all of the tumor-bearing mice treated with the Ebola virus, the mice still died, eventually, despite this extension in survival. Still, the researchers wrote that while intracranial injection of the altered Ebola virus produced “only a short-lived local infection” of normal cells, they concluded that the innate and adaptive immune systems in these mice are “fully capable of terminating the spread” of the virus within the brain.
Because Ebola infection appeared to target and eliminate tumors in many immunodeficient mice, the investigators concluded that the use of the virus “merits further testing in additional models of brain tumors.”1
References
- Zhang X, Zhang T, Davis JN, et al. Mucin-like domain of Ebola virus glycoprotein enhances selective oncolytic actions against brain tumors [published online February 12, 2020]. J Virol. doi: 10.1128/JVI.01967-19
- Hathaway B. Scientists find ally in fight against brain tumors: Ebola [press release]. New Haven, CT: Yale News. Published February 12, 2020. Accessed February 19, 2019.
