Glioblastomas are a very aggressive form of brain cancer that spread rapidly through the brain and to other parts of the body. They are often lethal because they are very difficult to treat. As I mentioned in my previous blog post, the first line of treatment for brain tumors is surgical removal of the tumor tissue, but this is complicated because it is difficult to identify which cells in the brain are cancerous and which are normal. Therefore, some cancerous cells often remain after surgery which can later grow and spread through the brain causing larger tumors to grow. Scientists at Yale University have procured an unlikely ally in the fight against glioblastomas: the Ebola virus. As Yale professor Anthony Van den Pol explains, “The irony is that one of the world’s deadliest viruses may be useful in treating one of the deadliest of brain cancers.“ 

Brain tumor scans

Brain Scans. Credit: Adobe Stock

“The irony is that one of the world’s deadliest viruses may be useful in treating one of the deadliest of brain cancers.“

 

You may have heard of how viruses can cause cancer – such as human papilloma virus (HPV), Epstein-Barr (herpes virus), Hepatitis B and C which have all been found to increase a patient’s risk for certain cancers. However, Dr. Van den Pol and other researchers have found that viruses could potentially be recruited for treatment of cancer.  

So, what do viruses have to do with cancer? First we need to understand the normal role of our immune system which is built to fight viruses.  

Normally, our cells can develop an innate immune response which is a defense system for our body against pathogens. When we are infected with pathogens, such as the Ebola virus or an influenza virus, normal cells are able to identify these ‘intruders’ and respond by sending immune cells (‘soldiers’) to the site of infection to kill and remove the intruders. However, cancer cells lack the ability to generate an innate immune response against invaders such as viruses. Hence, cancer researchers have been exploring the use of viruses to combat different types of cancer. The researchers have reasoned that if the cancer cells cannot defend themselves against viruses, then we can use the viruses as a way to selectively target cancer cells and kill them.  

Specifically, the vesicular stomatitis virus (VSV) has been shown as a virus that can enter brain tumor cells and reduce the size of brain tumors. However, this virus also invades normal cells, meaning it is too toxic as a treatment option. Therefore, researchers have investigated the possibility of including a part of the Ebola virus into the VSV to reduce the toxicity.

The Ebola virus (EBOV) is one of the most dangerous viruses, with a lethality approaching 90% in some outbreaks, meaning that 9 of the 10 people infected with the virus will die from it. Compare this to the approximate 2% lethality of the 2019 coronavirus outbreak and you realize how dangerous the EBOV is.

ebola virus

“Ebola Virus (green) on the cell’s surface” licensed under CC BY 2.0

So why are we considering the deadly EBOV for a possible treatment?

One of the main reasons why the EBOV is so lethal is because of specific characteristics exhibited by a stretch of protein (called a domain) on the virus. The presence of this domain constitutes one of several mechanisms by which EBOV successfully evades and delays activation of the host immune system. The domain is thought to act like an umbrella that shields the virus from attack by the host’s immune response.  This domain is also thought to play a role in the way that the Ebola virus spreads through the body: the EBOV infects many organs and cells of the body, but not the neurons. The neurons are cells that are a part of our nervous system in our brain, spinal cord and nerves. This unique characteristic of the Ebola virus to infect all cells, except those that are neuronal is important. Our brain is made up of neurons and glia – you can think of them as cogs and gears, both contributing to our brain’s functions. In glioblastoma, the brain cancer studied by these researchers, the glial cells are the ones which become cancerous. Therefore, the researchers incorporated the special domain of EBOV into the vesicular stomatitis virus (VSV). Their hope was that the addition of the special domain of EBOV would mean the new VSV-EBOV combination would selectively target glial cells over neurons. 

The results of this study showed that the presence of this special domain allowed the virus to enter tumorous brain cells at a 10X greater amount than when the domain was not incorporated. The researchers believe that this happened because the cancer cells in the brain already don’t have an ability to identify ‘invaders’ (i.e. the virus treatment), combined with the Ebola virus domain’s ability to selectively enter cancerous glial cells (rather than healthy neurons). Although this virus combination has been proven as safe (used to vaccinate a quarter million people in West Africa), there is still a lot more testing required to prove its ability to efficiently reduce tumors in the brain.  

For more information:

Xue Zhang, Tingting Zhang, John N. Davis, Andrea Marzi, Anthony M. Marchese, Michael D. Robek, Anthony N. van den Pol. Mucin-like domain of Ebola virus glycoprotein enhances selective oncolytic actions against brain tumors. Journal of Virology, 2020; DOI: 10.1128/JVI.01967-19