Using Zika virus to attack glioblastoma
Most research efforts aimed at Zika virus seek to kill the pathogen, which is known to cause brain defects in fetuses. But researchers at Washington University School of Medicine in St. Louis and the University of California at San Diego are turning the anti-Zika pursuit on its head, finding a potentially useful role for the virus in treating one of the deadliest brain cancers: glioblastoma.
Zika interferes with fetal brain development by targeting neural stem cells. These stem cells are generally less active in adult brains, which explains why getting bitten by a Zika-carrying mosquito isn’t dangerous for adults. The researchers figured they could take advantage of Zika’s preference for developing brain cells and use it to target glioblastoma stem cells.
So first they tried injecting mouse models of aggressive glioma with Zika virus. The virus slowed tumor growth and extended the animals’ lives, according to a press release. Then they tried an “attenuated” strain of the virus that was less potent. That also worked. And it worked even better when it was combined with the chemotherapy drug temozolomide. The research was published in the Journal of Experimental Medicine.
Using viruses against cancer is not a new idea: Amgen’s Imlygic, a modified form of the herpes virus, was the first such “oncolytic” virus to gain FDA approval and is now used in some patients with melanoma. Several researchers working in the oncolytic virus field are also pursuing combination strategies, pairing the pathogens with other immuno-oncology treatments or more traditional cancer drugs to see if a multipronged attack against tumors will be most effective.
But brain cancer has proven to be especially challenging, largely because neural stem cells promote tumor regrowth. "It is so frustrating to treat a patient as aggressively as we know how, only to see his or her tumor recur a few months later,” said co-author Milan Chheda, M.D., from Washington University School of Medicine in St. Louis in the release. “We wondered whether nature could provide a weapon to target the cells most likely responsible for this return."
Priming the immune system to attack and kill cancer is one of the approaches of interest to researchers who specialize in brain cancer. Last month, scientists at the University of Pennsylvania—one of the pioneers of the engineered immune cells known as CAR-T, which Novartis is now commercializing—reported data showing that CAR-T cells combined with checkpoint inhibitors may hold promise in treating glioblastoma. Researchers are also actively searching for more traditional treatments, such as antibodies. Earlier this year, Stanford spinout Forty Seven reported that its antibody Hu5F9-G4 shrunk tumors in five different mouse models of childhood brain cancer.
The authors of the Zika study note that in order to turn the virus into a therapy, more research is needed to determine whether attenuated strains could pose a public health risk by spreading or turning into more virulent pathogens. But because the naked virus is relatively harmless to adults, they believe any Zika-based therapy would likely prove to have an acceptable safety profile.