With the world’s media focusing on coronavirus, it’s easy to forget the former king, ebola, which dominated the world’s media from 2013 to 2016. People demanded quick diagnostics and vaccines against the novel threat to humanity. Looking back, Yale University researchers have applied their skills to exploit features of the ebola virus as an aid for combating another ruthless disease: brain cancer.
What prompted the scientists to use this specific virus as an anchor to their work, is its lack of interest in brain tissue. Although ebola virus infects a variety of organs, it shows relatively little attraction to the brain, thereby leaving victims systemically ill but cognitively aware. Ebola is significantly lethal because it evades the immune system, thus spreading throughout the body undetected. The host immune system is only activated when the infection is substantial, causing a fever so potent that it kills the individual. With so many risks, why would scientists even consider this as a potential therapy for brain tumours?
The research approach exploited the fact that brain cancer cells are unable to mount an immune response against viruses. This has fuelled research into the use of viruses to fight various cancers, a field known as Oncolytic Virus Therapy. This new era of cancer treatment falls at the fact that viruses can potentially introduce dangerous infections, which can kill the host organism faster than the cancer itself. Additionally, the host’s immune system can eliminate the helpful virus before it has the chance to reach the tumour.
Ebola virus intrigued Yale scientists as one of its seven genes allows it to avoid triggering an immune response. This gene is responsible for encoding a flag-like molecule on the surface of the virus, called a glycoprotein – an important structure to the virus. Researchers designed a novel “duo-virus” which contained the ebola virus glycoprotein, stuck onto the body of another virus, VSV – a lethal virus which usually infects domestic animals, although it can cause death in humans. The researchers inactivated the dangerous features of both viruses, resulting in an unlikely ally against glioblastomas, the deadliest of brain cancers.
Playing with fire, the scientists tested their novel treatment on mice which lacked their own immune system. They transplanted human glioblastoma cells into the brains of mice. Since there is no immune system in these mice, there is no rejection of foreign tissues. They found that intravenous delivery of the duo-virus showed efficient targeting and elimination of brain tumours and significant extension of survival of the mice. Furthermore, the destruction of cells was limited to those which were cancerous, and there was little infection of healthy brain cells.
It was important that the ebola virus glycoprotein in the duo-virus contained the important structural feature mentioned previously – it avoids triggering an immune response. Parallel experiments with a virus lacking this feature showed that it was unable to target the cancer specifically, and caused widespread infection of healthy brain tissue. Scientists are currently exploring the nature of this feature, identified as the “mucin-like domain”, and how it is able to distinguish between healthy and diseased tissue.
Researcher Anthony van den Pol spoke about the breaking discovery on Wednesday 12 February, in the Journal of Virology, describing the irony that “one of the world’s deadliest viruses may be useful in treating one of the deadliest of brain cancers.” The fact that we are able to take advantage of a virus which once wreaked havoc upon our lives is promising for the future of cancer research. It also offers a glimpse of hope in light of the inevitable COVID-19 pandemic, which may also, in a few years, be manipulated to offer a new solution to cancer therapy.