By Kathleen Berger Executive Producer for Science & Technology
Zika virus may be a key to unlocking the power of immunotherapy for glioblastoma, the most aggressive and deadly brain tumor. Glioblastoma is the most common and aggressive form of brain cancer. About 12,000 people are diagnosed each year in the U.S., and average survival time is only 14 months.
“Most people will die within two years of being diagnosed,” said Milan G. Chheda, MD, neuro-oncologist and associate professor of medicine at Washington University School of Medicine in St. Louis. “This field is really desperate for new treatments. The dream of neuro-oncologists has been to have a treatment that can specifically target these otherwise resistant cells.”
One new treatment is using Zika virus. The discovery was made at Washington University School of Medicine through a collaboration between Chheda’s lab and the lab of Michael Diamond, MD, PhD, professor of medicine and professor of molecular microbiology, and of pathology & immunology.
Diamond previously published extensive research on the Zika virus, a disease that spread to people through mosquito bites. Outbreaks of Zika left many babies with permanent brain damage. As scary as Zika may be, research on Zika soon led to an idea about trying to use the Zika virus in the brain to treat glioblastoma. The idea revealed how Zika could be a silver lining for adult patients with this deadly brain tumor.
“The virus has a propensity to infect neural progenitor cells in fetuses, then can cause cell injury to them. Because of that, we had a former postdoc in the laboratory who had an idea and said, ‘Well if it can infect progenitor cells that are functioning normally, what about tumor stem cells in the brain that sort of look like progenitor cells?’ They’re a little different, they’re tumor cells, but they share some features with them. And so what he showed was that Zika virus could infect and kill tumor stem cells that are glioblastoma tumor stem cells,” said Diamond.
“We wanted to see if it’s going to just kill any cell that we subject it to, and it doesn’t. It’s very specific against cancer stem cells,” said Chheda. “When we injected it directly into growing tumors in mice, we found that these mice could survive long term. When you don’t use the virus, in these control groups, they would die within about a month or just over a month. But (with Zika virus injections) we were seeing mice living years. And so these are long-term survivor mice,” said Chheda.
They discovered how Zika virus gives a powerful boost to immunotherapy. Immunotherapy uses a patient’s immune system to fight cancer. In lab mice, Diamond’s team discovered how the Zika virus can activate immune cells to destroy the deadly brain tumor.
“First of all, we made it in a more attenuated version (of the Zika virus) that’s safer because you know there’s some concerns about putting viruses in the brains of immunocompromised people. So we engineered a way that the virus is not nearly as potent as it normally is, but still can kill all of these stem cells,” said Diamond. “The major way that the virus works is actually to reawaken the immune response because the combination of the virus and the tumor provoke a CD8+ T cell response and it’s the CD8+ T cell response that then clears the rest of the tumor away.”
The groundbreaking findings may one day be used as a targeted therapy for glioblastoma.
“The first treatment for glioblastoma is usually a surgical resection. Now (the idea would be) we can combine Zika virus with immunotherapy at the time and right after the tumor is removed,” said Diamond. “And so at the time that you get this resection, the surgeon would actually introduced Zika virus directly into the glioblastoma cavity. They would put the virus directly into the brain. And then maybe a couple of days later, a week later, we might add some other drugs to go with it, for example, checkpoint blockade inhibitors which have been shown to accelerate tumor clearance in certain solid tumors but had not really worked in glioblastoma.”
However, Diamond said the drugs gave outstanding results treating glioblastoma in animal models when combined with the Zika virus injection. For such a treatment to be possible, animal studies continue.