A new study shows the Zika virus kills brain cancer stem cells—the kind of cells most resistant to standard treatments.
The findings suggest the lethal power of the virus could be directed at malignant cells in the brain—and potentially improve the chances of people with glioblastoma—that is most often fatal within a year of diagnosis.
“We showed that Zika virus can kill the kind of glioblastoma cells that tend to be resistant to current treatments and lead to death,” says Michael S. Diamond, professor of medicine at Washington University School of Medicine and the study’s co-senior author.
Each year in the United States, about 12,000 people are diagnosed with glioblastoma, the most common form of brain cancer.
The standard treatment is aggressive—surgery, followed by chemotherapy and radiation. But, most tumors still 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 drugs.
Smaller tumors, longer lives
In their neurological origins and near-limitless ability to create new cells, glioblastoma stem cells reminded postdoctoral researcher Zhe Zhu of neuroprogenitor cells, which generate cells for the growing brain. Zika virus specifically targets and kills neuroprogenitor cells.
For a new study that appears in the Journal of Experimental Medicine, researchers tested whether the virus could kill stem cells in glioblastomas removed from patients at diagnosis. They infected tumors with one of two strains of Zika virus. Both strains spread through the tumors, infecting and killing the cancer stem cells while largely avoiding other tumor cells.
The findings suggest that Zika infection and chemotherapy-radiation treatment have complementary effects. The standard treatment kills the bulk of the tumor cells but often leaves the stem cells intact to regenerate the tumor. Zika virus attacks the stem cells but bypasses the greater part of the tumor.
“We see Zika one day being used in combination with current therapies to eradicate the whole tumor,” says co-senior author Milan G. Chheda, assistant professor of medicine and of neurology.
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 tumors of 18 and 15 mice, respectively.
Tumors 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 fetal brain, on the other hand, is loaded with these 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.
Additional studies of the virus using brain tissue from epilepsy patients showed the virus doesn’t 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 defense 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, the original strain was more potent, but the mutant strain also succeeded in killing the cancerous cells.
“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 Diamond, who is also 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.”
Researchers from the University of California, San Diego are coauthors of the study. The National Institutes of Health, the Pardee Foundation, the Concern Foundation, the Cancer Research Foundation, and the McDonnell Center for Cellular and Molecular Neurobiology of Washington University funded the work.