Researchers found a Zika virus, which is spread by mosquitoes, successfully killed off human glioblastoma brain cancer stem cells transplanted into mice. Photo by mycteria-shutterstock
Sept. 18 (UPI) -- A Zika virus successfully killed off human glioblastoma brain cancer stem cells transplanted into mice, according to a study.
Based upon the results, researchers believe a live, attenuated version of the Zika virus, which is spread by mosquitoes, could be used as an option for treatment of the incurable form of brain cancer. The findings were published Tuesday in the journal mBio.
Glioblastoma accounts for 15 percent of all brain tumors, and patients have a median survival time of approximately 14.6 months, according to the American Brain Tumor Association. U.S. Sens. John McCain and Ted Kennedy died from the disease.
Despite surgery, radiation and chemotherapy, patients experience a high recurrence rate of their cancer. This recurrence is possibly due to cancer stem cells, called glioblastoma stem cells, which are hidden in nearby brain tissue even after the combination of therapies.
"During the Zika epidemic [in 2015-16], we learned that the virus preferentially infects neural progenitor cells in the fetus, and causes the devastating microcephaly seen in babies born to infected mothers," Dr. Pei-Yong Shi, a virologist at University of Texas Medical Branch in Galveston, said in a press release. "We made the connection that perhaps Zika virus could also specifically infect the GSCs."
Previously, Shi and his collaborators at Washington University in St. Louis found that the Zika virus did indeed attack and kill GSCs grown in the lab, as well as in a mouse study of glioblastoma.
The Zika virus also was much less efficient at attacking the differentiated, healthy brain cells, the researchers said.
"As a virologist, I see that we should take advantage of the 'bad' side of viruses," Shi said. "They should have a role to play in cancer treatment."
The researchers first wanted to see if there is a safe way to use Zika virus in patients to attack cancer cells.
They developed a promising live-attenuated Zika vaccine candidate called ZIKV-LAV that safely and effectively protected against infection in mice and non-human primates. When ZIKV-LAV was injected into the brains of mice, there were no health effects, no weight loss and no behavioral abnormalities in them.
The researchers then needed to determine whether ZIKV-LAV could work to infect and kill human patient-derived GSCs in mice. They mixed GSCs from two different human patient donors with the ZIKV-LAV and injected the mixture into the brains of mice.
Mice that got the ZIKV-LAV injection saw a significant delay in tumor development. And co-implanting the virus along with the GSCs also prolonged the median survival time of the treated mice to around 50 days, compared to around 30 days for the untreated mice who received GSCs alone.
The team then investigated the cellular mechanisms that the modified Zika virus used to kill the GSCs. In the treated cells, they found the virus triggered a strong antiviral response in the cells, which induced inflammation and eventually cell death.
They next plan to develop safety tests of the ZIKV-LAV in glioblastoma patients.
"The good balance between the safety of ZIKV-LAV and its efficacy against human GSCs suggests that it is a potential candidate for combination with the current treatment regimen for GBM therapy," the researchers wrote.