Infectious Diseases

Zika enlisted for the fight against brain cancer

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On the left are the brain cancer cells before being treated with the Zika virus and on the right is after the treatment
Zhe Zhu
Transmission electron microscope image of negative-stained, Fortaleza-strain Zika virus (red)
National Institute of Allergy and Infectious Diseases (NIAID)
On the left are the brain cancer cells before being treated with the Zika virus and on the right is after the treatment
Zhe Zhu

For well over half a century, scientists have been working to harness the cell-destroying power of viruses in the battle against cancer. The latest addition to this arsenal comes from an unlikely source, the relatively new Zika virus, which could offer a new way to fight deadly brain cancers.

A virus that is found to target and kill cancer cells is known as an oncolytic virus, and over the years scientists have worked to engineer a number of different viral strains with this ability. The biggest challenge faced by scientists in the field has been finding ways to manipulate the viruses into a state that makes them safe to use in a clinical environment, but retains their effectiveness as a cancer-killing agent.

Research in the field slowed down markedly in the late 20th century, with technology at the time unable to adequately engineer custom viruses, but genetic advances over the past couple of decades have reinvigorated the field. The first oncolytic virus to be approved for therapy came a little over a decade ago when the herpes simplex virus was harnessed to develop a treatment for head and neck cancers. Since then the field has boomed, with a couple of dozen different clinical trials currently underway, working with a variety of viral strains.

This latest research began when a group of researchers wondered if the activity of the new Zika virus could be leveraged to kill glioblastomas, a lethal form of brain cancer. This kind of brain cancer has proved challenging to effectively treat because, even after the major tumors are surgically removed and treated with chemotherapy, a small population of glioblastoma stem cells still tend to remain, causing the cancer to swiftly regrow.

These glioblastoma stem cells share a distinct similarity with neuroprogenitor cells, the cells that help grow the brain. The Zika virus, which has proved to be relatively harmless in adults, is extremely dangerous for pregnant women, as it targets and kills these neuroprogenitor cells. The virus can infect a fetus, destroying its developing brain, resulting in major birth defects and brain damage.

Transmission electron microscope image of negative-stained, Fortaleza-strain Zika virus (red)
National Institute of Allergy and Infectious Diseases (NIAID)

Researchers from the Washington University School of Medicine in St. Louis and the University of California San Diego School of Medicine set out to discover whether the Zika virus could specifically target and kill these cancerous stem cells while leaving noncancerous brain cells alone. After successfully testing the viruses effect on these cancer cells in vitro, the researchers moved to live animal tests. Two weeks after the virus was injected directly into the brain tumors of mice, the tumors were found to be significantly reduced.

The team still faces several challenges before moving forward with the research. Primarily, the virus needs to be further engineered to reduce its broader virality. Early experiments have already weakened the defensive functions of the virus so that if it spreads to healthy cells, it would be easily destroyed by the body's immune system.

"We're going to introduce additional mutations to sensitize the virus even more to the innate immune response and prevent the infection from spreading," says the study's co-senior author Michael Diamond. "Once we add a few more changes, I think it's going to be impossible for the virus to overcome them and cause disease."

Needless to say, this research is still at a very early stage. It is unknown how the virus will act when introduced into the tumor of a living human being, and any Zika-based treatment would inevitably have to undergo extensive trials to evaluate safety. But, this is yet another exciting addition into a burgeoning field that would allow formerly lethal viruses to be used to heal instead of harm.

The research was published in the Journal of Experimental Medicine.

Source: Washington University School of Medicine in St Louis

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