The Zika virus can activate immune cells to destroy an aggressive brain cancer in mice, giving a powerful boost to an immunotherapy drug and sparking long-lasting immunological memory that can ward off tumor recurrence for at least 18 months, according to a study posted on the website of Washington University School of Medicine in St. Louis on Wednesday.
To better understand how Zika virus works against brain cancer, researchers at the university transplanted brain cancer cells into the brains of mice. One week later, they injected Zika virus into the mice’s quickly growing tumors, or sterile saltwater for comparison.
The results show that Zika virus treatment improved the animals’ chance of survival dramatically: from 10 percent to 63 percent for one cancer cell line, and from zero percent to 37 percent for the other.
Further analysis showed that the virus had attracted large numbers of immune cells of many kinds to the tumors, most importantly so-called cytotoxic T cells, a type of immune cell specialized for killing cancerous cells. What’s more, Zika virus treatment induced lasting immunological memory.
The researchers re-introduced the tumor into the other side of the mice’s brains a year and a half after the original tumor. All but one of the mice destroyed the new tumor within a few weeks.
Many tumors create suppressive environments around themselves that hinder an effective immune response. The suppression is created, in part, by so-called immune checkpoint molecules such as PD-1 that keep immune cells that kill cancer cells, called cytotoxic T cells, turned “off” and unable to attack.
Immunotherapy drugs that target PD-1 have been used successfully to treat skin, blood, lung and other cancers. But the immunotherapy drugs do not work with glioblastoma.
“Glioblastoma is a difficult disease because it progresses so quickly, and we don’t have any interventions that ultimately alter its course,” said co-senior author Milan Chheda, an assistant professor of medicine and of neurology.
“We can treat the initial tumor, but recurrence is quick and inevitable. By using Zika virus, we’re revving up the immune system to respond to an otherwise ineffective immunotherapy.
This also sets the stage to prevent recurrence, allowing us to overcome two major barriers to effective treatment.”
The results are promising, but Zika virus is best known for causing brain damage in fetuses, so any therapy that involves putting the virus in people’s brains raises safety concerns.
Glioblastoma is the most common and aggressive form of brain cancer. About 12,000 people are diagnosed each year in the United States, and average survival time is only 14 months.The findings have been published online in the journal JCI Insight.