Oncolytic Therapy Cures Glioblastoma in Model

Results of experiments conducted using a mouse glioblastoma model suggest that treatment with Zika virus could be used to treat this aggressive and usual fatal disease.

Glioblastoma is the most common primary tumor of the central nervous system and is almost always fatal. The aggressive invasion of glioblastoma cells into the surrounding normal brain makes complete surgical removal impossible, significantly increases resistance to the standard therapy regimen, and virtually assures tumor recurrence. Treatment of glioblastoma usually comprises surgical removal of the tumor followed by radiation treatment and chemotherapy using the drug temozolomide (TMZ). However, the penetration of the tumor into adjacent brain tissue prevents the surgical removal of all tumor cells, which usually develop resistance to TMZ. While immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other types of cancer, glioblastomas have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. MDSCs contribute to an immunosuppressive network that protects tumors by disabling T-cell adaptive immunity.

In a novel approach toward treating glioblastoma, investigators at the Washington University School of Medicine (St. Louis, MO, USA) and the University of California, San Diego (USA) explored the use of oncolytic virus therapy with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus.

The investigators reported in the September 5, 2017, online edition of The Journal of Experimental Medicine that ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells.

ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV.

"We hypothesized that the preference of Zika virus for neural precursor cells could be leveraged against glioblastoma stem cells," said contributing author Dr. Michael Diamond, professor of molecular microbiology, pathology, and immunology at the Washington University School of Medicine. "Our study is a first step toward the development of safe and effective strains of Zika virus that could become important tools in neuro-oncology and the treatment of glioblastoma. However, public health concerns will need to be addressed through preclinical testing and evaluations of the strains' ability to disseminate or revert to more virulent forms."

Related Links:
Washington University School of Medicine
University of California, San Diego