Zika-based therapy for metastatic neuroblastoma with Tamarah Westmoreland, MD and Joseph Mazar, PhD

At the 2025 Pediatric Academic Societies Meeting, Joseph Mazar, PhD, and Tamarah Westmoreland, MD, FAAP, presented findings on the therapeutic potential of Zika virus in treating metastatic high-risk neuroblastoma. The session, titled "The Zika Viral Therapy of Metastatic High-Risk Neuroblastoma In Vivo Models Yields Effective Tumor Elimination when Applied to Permissive Host Cells," explored how Zika-based therapy could offer a novel solution for a cancer with historically low survival outcomes.

"Our lab has studied high-risk neuroblastoma for years because the 5-year overall survival, even with intensive therapy, is not where we need it to be," said Westmoreland, a pediatric surgeon at Nemours Children's Health and professor of surgery at the University of Central Florida College of Medicine. "It is around 40 to 50%." Early work from their lab demonstrated that direct injection of Zika virus into neuroblastoma tumors in mice eliminated tumors and extended survival, findings that led to this more advanced investigation.

The study tested whether Zika virus could be used to treat metastatic disease, where multiple tumors are present and not all are easily accessible. "We tried this model of introducing a tumor onto one side of the mouse and the Zika onto the other... and what we found is that doesn't work at all," said Mazar, research scientist and assistant professor at Nemours Children’s Health. "But when we introduced the virus locally into one tumor, we found that the majority of the tumors on the other side of the mouse were eliminated."

This effect appeared to be because of viral replication within the permissive tumor, which then acted as a source of Zika particles capable of reaching and destroying other tumor sites. "You're effectively weaponizing one tumor to kill the others," Mazar noted. The implication is that even if only one tumor site is accessible, it may be enough to initiate systemic therapeutic benefit.

The investigators emphasized Zika’s clinical promise as a naturally attenuated virus. "In humans, it primarily manifests as a cold if you have symptoms at all, and that normally resolves in around two weeks," Westmoreland explained. Moreover, shedding studies showed that the virus was typically cleared within 7 to 10 days. "It doesn't induce inflammation, and the host... remain asymptomatic," added Mazar.

While this approach has yet to be tested in humans, Westmoreland noted the significance of thinking outside traditional treatment paradigms. "We need some difference, out-of-the-box novel treatment to help when we're not achieving the overall long-term survival that we all want to see."

Reference:

The Zika Viral Therapy of Metastatic High-Risk Neuroblastoma In Vivo Models yields effective Tumor Elimination when Applied to Permissive Host Cells. Session. Presented at: