In a paper published in Cancer Research, researchers at the University of Sao Paulo suggested that Zika virus could be used to treat embryonal CNS tumors.
Embryonal CNS tumors, which typically occur in infants, arise from defects in neural stem and progenitor cells during embryonic development. The tumors are made up of cancer stem cells, which have neural stem-like features and are resistant to standard cancer therapies.
The researchers first observed that Brazilian Zika virus killed human embryonal CNS tumor cell lines, but had little effect on breast, prostate and colorectal cancer lines. The researchers noted that Zika infected tumor cells more than normal neural cells when the embryonal CNS cancer cell lines were cultured with neural progenitor cells.
In xenograft mouse models of embryonal CNS tumors, injection of the virus into cerebral ventricles improved overall survival, reduced tumor burden and metastases and led to remission in 20 of 29 animals.
In a cross-infection experiment, the researchers infected normal neural stem and progenitor cells with embryonal CNS tumor cells previously infected with Brazilian Zika virus, and found the neural stem and progenitor cells produced few or no functional viral particles. The authors wrote that the virus’ requirement for alive and fully functional host cells could explain its lower replication in tumor cells.
Previous research in the Journal of Experimental Medicine from Washington University School of Medicine in St. Louis and colleagues showed Zika virus killed glioblastoma stem cells and increased survival in mice with glioblastoma. That paper’s authors found that an attenuated Zika virus was also able to decrease growth in three glioblastoma stem cell lines.
The Brazilian researchers suggested future work should investigate whether attenuated versions of the Zika virus could avoid adverse effects and neutralization by the host immune system. Lead authors and University of Sao Paulo professors Oswaldo Okamoto and Mayana Zatz told BioCentury the team does not have plans to develop an attenuated form of Zika virus but may consider testing an attenuated virus in the future.
Okamoto and Zatz said the finding that CNS tumor cells produce defective viral particles that are not capable of infecting normal cells “could favor safety” and decrease the likelihood that infectious viral particles will propagate to other organs.