Zika virus shown to kill brain cancer stem cells

Zika virus has been shown to kill brain cancer stem cells, suggesting it could prove an effective treatment for glioblastoma.

Researchers from Washington University School of Medicine and the University of California San Diego School of Medicine tested whether the virus could kill stem cells in glioblastomas removed from patients at diagnosis. They infected tumours with one of two strains of Zika virus. Both strains spread through the tumours, infecting and killing the cancer stem cells while largely avoiding other tumour cells.

The findings, published in The Journal of Experimental Medicine suggest that Zika infection and chemotherapy-radiation treatment have complementary effects. The standard treatment kills the bulk of the tumour cells but often leaves the stem cells intact to regenerate the tumour. Zika virus attacks the stem cells but bypasses the greater part of the tumour.

“We see Zika one day being used in combination with current therapies to eradicate the whole tumor,” said Milan Chheda, senior co-author from the Washington University School of Medicine.

Each year in the United States, about 12,000 people are diagnosed with glioblastoma, the most common form of brain cancer, which is most often fatal within a year of diagnosis. The standard treatment is aggressive – surgery, followed by chemotherapy and radiation – yet most tumors recur within six months. A small population of cells, known as glioblastoma stem cells, often survives the onslaught and continues to divide, producing new tumor cells to replace the ones killed by the cancer drugs.

To find out whether the virus could help treat cancer in a living animal, the researchers injected either Zika virus or a saltwater placebo directly into the brain tumours of 18 and 15 mice, respectively. Tumours were significantly smaller in the Zika-treated mice two weeks after injection, and those mice survived significantly longer than the ones given saltwater.

If Zika were used in people, it would have to be injected into the brain, most likely during surgery to remove the primary tumor. If introduced through another part of the body, the person’s immune system would sweep it away before it could reach the brain.

The idea of injecting a virus notorious for causing brain damage into people’s brains seems alarming, but Zika may be safer for use in adults because its primary targets – neuroprogenitor cells – are rare in the adult brain. The foetal brain, in contrast, is loaded with such cells, which is part of the reason why Zika infection before birth produces widespread and severe brain damage, while natural infection in adulthood causes mild symptoms.

The researchers conducted additional studies of the virus using brain tissue from epilepsy patients and showed that the virus does not infect noncancerous brain cells.

As an additional safety feature, the researchers introduced two mutations that weakened the virus’s ability to combat the cell’s defenses against infection, reasoning that the mutated virus still would be able to grow in tumor cells – which have a poor antiviral defence system  but would be eliminated quickly in healthy cells with a robust antiviral response.

When they tested the mutant viral strain and the original parental strain in glioblastoma stem cells, they found that the original strain was more potent, but that the mutant strain also succeeded in killing the cancerous cells.

“We’re going to introduce additional mutations to sensitise the virus even more to the innate immune response and prevent the infection from spreading,” said Diamond, who also is a professor of molecular microbiology, and of pathology and immunology. “Once we add a few more changes, I think it’s going to be impossible for the virus to overcome them and cause disease.”