Using Zika virus to treat neuroblastoma in children

Zika virus is notorious for causing brain defects when passed down from a pregnant woman to her fetus. But researchers at Nemours Children’s Hospital and the University of Central Florida suggest that the exact ability of the virus to infect developing nerve cells might help fight neuroblastoma, a rare but deadly childhood cancer.

Past studies have shown that Zika is likely targeting neural progenitors—cells that are more developed than stem cells but can also generate neuronal and glial cells of the nervous system. It just happens that neuroblastoma also starts in these immature nerve cells. 

In their study, the scientists first tested Zika’s effect in several human neuroblastoma cell lines. All but one cell line responded well to Zika infection and died in massive amounts, researchers reported in the Journal Plos One

"The same thing that makes Zika so detrimental to developing infants gives it promise as a cancer treatment. Its attack on developing nerve cells, the same type of cells neuroblastoma develops from, allows the virus to target these cancer cells and leave normal cells alone," said Kenneth Alexander, M.D., Ph.D., Nemours’ chief of the Division of Infectious Diseases, in a statement.

What happened to that one aberrant cell type? The team observed that one cell type that's responsive to Zika virus infection expresses a glycoprotein called CD24, while the nonresponsive cell line does not express it. So they suspect that CD24 is necessary for Zika to destroy human neuroblastoma cells. Scientists then verified their hypothesis through further tests that knocked in or out CD24 expression in those two cell lines.

CD24 is commonly expressed on primitive nerve cells and is also highly expressed in neuroblastoma. But it isn't present in mature cells, which probably explains why Zika only causes mild or asymptomatic infections in children and adults but can be detrimental to developing fetuses.

Because of that trait, the team proposed in the study that "therapeutic Zika virus infection of individuals with CD24-positive tumors could result in selective tumor cell infection and lysis."

The idea of using viruses to treat cancer has been around for a while. In fact, scientists have tested measles, adenovirus and polio in brain cancer. A recent study published in the Journal of Experimental Medicine also showed promising results treating glioblastoma with the virus in mice. And a team at the University of São Paulo in Brazil successfully treated a small number of mice with two types of childhood brain tumors using Zika.

Neuroblastoma accounts for only 6% of all childhood cancers, but it causes a disproportionately high 15% of childhood cancer deaths. Since CD24 is also found on other human tumors, the prospect of Zika-based therapy could be attractive in other pediatric cancers and even adult tumors, the researchers at Nemours and the University of Central Florida argue.

The team is currently validating their findings in animal models and suggests that "the minimal pathogenic effects of natural Zika virus infection in children offers the prospect of a therapy devoid of the long-term toxic effects of standard surgery, chemotherapy, and radiation."

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