1. Zika virus has oncolytic activity against glioblastoma stem cells.
- Author
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Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, Fernandez E, Richner JM, Zhang R, Shan C, Tycksen E, Wang X, Shi PY, Diamond MS, Rich JN, and Chheda MG
- Subjects
- Animals, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms therapy, Cell Line, Tumor, Cell Proliferation, Chlorocebus aethiops, Combined Modality Therapy, Dacarbazine analogs & derivatives, Dacarbazine therapeutic use, Female, Fluorescent Antibody Technique, Glioblastoma therapy, Humans, Mice, Mice, Inbred C57BL, Neoplasms, Experimental therapy, Neoplasms, Experimental virology, Temozolomide, Vero Cells, Brain Neoplasms virology, Glioblastoma virology, Neoplastic Stem Cells virology, Oncolytic Virotherapy methods, Zika Virus physiology
- Abstract
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. 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. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients., (© 2017 Zhu et al.)
- Published
- 2017
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