Glioblastoma Stem Cells May Be No Match for the Zika Virus

In an ironic turn of events, it seems that the Zika virus, which has devastating effects on the brains of newborn infants, may, in fact, be able to kill the stem cells of one of the deadliest forms of cancer in adults: glioblastoma. These findings come from research conducted at the Washington University School of Medicine in St. Louis and the University of California San Diego School of Medicine, and published in The Journal of Experimental Medicine.

According to the official press release from Washington University, about 12,000 individuals are diagnosed with glioblastoma in the United States, each year, US Senator John McCain among them. Treatment for the disease typically includes surgery, chemotherapy, and radiation; however, tumors are known to recur within 6 months. This is thought to be because “a small population of cells, known as glioblastoma stem cells, often survives the [treatment] and continues to divide, producing new tumor cells to replace the ones killed by the cancer drugs,” according to the press release. The average lifespan for an individual after diagnosis is 1 year.

The cancer’s ability to create new cells, however, led first author and postdoctoral researcher Zhe Zhu, PhD, from University of California San Diego, to think about “neuroprogenitor cells, which generate cells for the growing brain.” These same cells are targeted and killed by the Zika virus. To learn whether the virus would effectively kill the glioblastoma stem cells, the researchers, “injected tumors removed from patients at diagnosis [with glioblastoma] with 1 of 2 strains of the Zika virus,” according to the press release. The findings showed that both strains of the virus were competent at killing the stem cells, while avoiding other tumor cells.

Based on these results, the researchers concluded that the Zika virus may be able to work in conjunction with chemotherapy and radiation to completely eradicate the tumor, with the virus killing the stems cells and the standard therapy taking care of the rest. To this end, co-senior author Milan G. Chheda, MD, of Washington University School of Medicine, was quoted in the press release as saying, “We see Zika one day being used in combination with current therapies to eradicate the whole tumor.”

The researchers also tested the ability of the virus to work against cancer in living animals by injecting it into brain tumors of 18 mice. (For control, 15 additional mice with brain tumors were injected with placebo.) After 2 weeks, the mice injected with the Zika virus had significantly smaller tumors and a longer survival rate than the mice injected with placebo. Additional studies that used brain tissue collected from epilepsy patients also revealed that noncancerous brain cells were not infected by the virus.

To be able to use the treatment in humans, the Zika virus would need to be injected directly into the brain, “most likely during surgery to remove the primary tumor,” according to the press release. If the virus were introduced “through another part of the body, the person's immune system would sweep it away before it could reach the brain.”

Although the act of injecting the Zika virus directly into the brain would seem to be counterintuitive, given the virus’ ability to cause brain damage in infants, neuroprogenitor cells—the virus’ primary target—are more abundant in the fetal brain than the adult brain. This makes the virus potentially safer to use in adults, in whom the virus causes usually only mild symptoms.

To make the virus safer, 2 mutations were introduced that weakened its ability to fight cell’s defense systems. This mutation still allowed the virus to grow inside of the tumor cells, but rendered it weak enough that healthy cells would quickly be able to destroy it. Although weaker, the (safer) mutated virus was found to still be able to kill the cancer cells.

Michael S. Diamond, MD, PhD, from the Herbert S. Gasser Professor of Medicine at Washington University School of Medicine, and senior co-author on the study remarked on these changes to the virus in the press release, stating, “We're going to introduce additional mutations to sensitize the virus even more to the innate immune response and prevent the infection from spreading. Once we add a few more changes, I think it's going to be impossible for the virus to overcome them and cause disease.”

These cancer-killing capabilities seem to be unique to the Zika virus; for example, the researchers “found that West Nile virus indiscriminately killed both tumor and normal neural cells.” Thus, as an oncolytic virus, Zika has the potential to be modified and used as a complimentary therapy against glioblastoma in adults, in the future.