As the world discovered in 2016, the seemingly benign Zika virus is capable of inflicting life-altering damage when it finds its way into the developing brains of fetuses. Now scientists hope to harness that horrible potential as a weapon to fight cancer.
Several research groups are exploring whether Zika viruses could be unleashed on cancers, effectively wiping out the dangerous cells of a brain or central nervous system cancer. One group, at Nemours Children’s Hospital in Orlando, published findings of early-stage work Wednesday in the journal PLOS One.
The research, done in cancer cell lines, showed that the virus was highly effective in killing cells of most neuroblastomas, the most common form of cancer in young children. An exception — the virus was not lethal to the cells in one neuroblastoma cell line — provided the group with important insights into when the therapy would be effective, the researchers said.
The group expressed excitement at the potential of the Zika virus to be a potent cancer fighter, suggesting that at one point it might be used in conjunction with surgeries, to mop up any lingering cancer cells not extracted during the removal of tumors.
“We may not be able to see them, but the virus will act like a smart missile and go right for them — whereas all the surrounding tissue that is normal will be ignored,” said lead author Joseph Mazar, a scientist in the department of biomedical research at Nemours Children’s.
Neuroblastomas are cancers that develop in neuroblasts, the embryonic cells that form the network of nerve fibers that make up the central nervous system. About 800 children a year in the United States are diagnosed with neuroblastoma, according to the American Cancer Society.
The cancers can form along the spine or in the adrenal glands. Most are diagnosed before the age of 5 and few of these cancers are found in children over the age of 10.
The overall five-year survival rate for neuroblastoma is 79 percent, but can be as low as 40 percent to 50 percent in high-risk cases.
Dr. Kenneth Alexander, chief of infectious diseases at Nemours Children’s, was reading a scientific paper that reported on the type of cells Zika targeted when it attacked fetal brains — neuroblasts. That made sense, given the damage the virus caused, he said. Fetal brains are full of neuroblasts.
But he also drew a line between the finding and neuroblastomas. The line was both theoretical and geographic — Alexander’s lab is located beside that of senior author Dr. Tamarah Westmoreland, a surgeon who researches neuroblastoma. He raised the idea with her and a project was born.
The fact the virus is drawn to cells that are dividing and differentiating — true both of neuroblasts and of some cancer cells — made Zika seem like an obvious choice as an oncolytic (cancer-fighting) virus. It seemed likely Zika would attack the cells that needed to be killed, without also turning on healthy tissues.
“It targets more the developing or progenitor-like cells, which neuroblastoma is, instead of targeting the more mature cells. And that’s what makes it more targeted,” Westmoreland said.
The group has just started testing the work further in mice and will move later into primates, she said.
The idea of using viruses to fight cancers has been around for decades; Mazar noted it arose from observations that some cancer patients experienced a regression of their tumors after viral infections.
A number of viruses have been studied as possible cancer therapies. But many have safety side effects that have limited their utility. And this work has always involved modifying the viruses to limit their ability to cause side effects or to continue to multiply in the body.
Mazar wondered if Zika, which causes mild infections that the body clears quickly in most cases, could be used without modifications — in scientific terms, in its wild-type form.
But Dr. Jeremy Rich, who is also studying Zika’s potential as an oncolytic, insisted that is unlikely to be allowed. For safety reasons — both from the point of view of the individual patient and the potential that this type of treatment might lead to transmission of Zika to others — the Food and Drug Administration would likely object, Rich told STAT.
“There’s no way the FDA will allow them or us or anyone else to use wild-type virus at this point. It will not happen,” said Rich, director of neuro-oncology, and of the Brain Tumor Institute of the University of California San Diego Health.
Rich, who was not involved in this new study, has been working with a team of scientists at Washington University School of Medicine to identify mutations that would render Zika safer to use as a cancer fighter. Last fall, they published a paper reporting that Zika was effective in killing glioblastoma cells. Glioblastoma, which is the cancer diagnosed in Sen. John McCain, is an aggressive form of brain cancer that is often fatal.
Rich noted that the Florida group’s work showed that one of the cell lines was not killed by the Zika virus. The Nemours researchers suggested that was because those cells lacked a protein on their surface, CD24, that was found in the other tumor cells.
The unaffected cell line was taken from a tumor that had already been treated and had developed resistance, Westmoreland noted. Both her group and Rich suggested if the Zika virus is eventually approved as a cancer therapy, it would be critical to test for the presence of CD24 before using it on a cancer.
Both groups are exploring Zika’s potential, suggesting it may extend beyond glioblastomas and neuroblastomas.