Targeting glioblastoma using oncolytic viruses delivered by human pluripotent stem cell-derived neural progenitor cells

利用人多能干细胞衍生的神经祖细胞递送溶瘤病毒靶向治疗胶质母细胞瘤

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Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor that has no cure. Oncolytic virotherapy is emerging as an effective approach to target cancer cells. Here, we show that the CF17 oncolytic virus, either delivered directly or by human pluripotent stem cell (hPSC)-derived neural progenitor cell (NPC) carrier, exerts strong growth inhibitory effect on GBM stem cells (GSCs) in vitro. More tumor cells were targeted by oncolytic virus in NPC-carried CF17-GFP-treated brains than that in CF17-GFP alone-treated brains, and more reduction in the tumor cell number was detected in CF17-GFP-NPC-treated mouse brains, compared to CF17-GFP alone-treated brains 7 days after treatment. Moreover, we show that CF17, either delivered directly or carried by NPCs, can suppress GSC-derived GBM tumor progression and prolong the survival of tumor-bearing mice substantially in a GBM mouse model. Therefore, our study identifies the CF17 oncolytic virus as a promising therapeutic candidate for GBM in more than one way of delivery.

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