MODL-06. ASSESSMENT OF ONCOLYTIC VIRUS SPECIFICITY AND CYTOTOXICITY IN A HYBRID GLIOBLASTOMA-CEREBRAL ORGANOID MODEL

Abstract Recent studies have demonstrated potent oncolytic effects of wild-type Zika virus (ZIKV) against primary central nervous system (CNS) tumors, including Medulloblastoma, Atypical Teratoid/Rhabdoid Tumor (AT/RT), and Glioblastoma (GBM). However, the neurotropism ZIKV urges further evaluation specific tumor-targeting properties comparative toxicity to non-neoplastic neural cells in order address its therapeutic potential. We developed a hybrid organoid model by co-culturing GBM with mature human cerebral organoids assessed cytotoxicity Brazilian isolate (ZIKVBR) towards normal brain cells. Human induced pluripotent stem (hiPSC)-derived were co-cultured 105 GFP-expressing three different cell lines. A total 20.000 PFU ZIKVBR or mock condition was added per model. Viable analyzed flow cytometry (FC) fluorescence microscopy at time points. presence assay. Although infection did not cause pronounced reduction GFP+ proportion over all lines, viability analysis showed greater amount non-viable GFP- ZIKVBR-treated groups, compared their corresponding groups. assays culture supernatants confirmed infectious viral particles treated groups absence Our data reveal that has potential effect characterized preferential killing tumor cells, These findings support development an therapy platform based on ZIKV.