Abstract
A glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OVT) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the oncolytic virus (OV) is applied intratumorally. Using two xenograft GBM mouse models and immunofluorescence analyses, we investigated the intranasal delivery of the oncolytic adenovirus (OAV) XVir-N-31 via virus-loaded, optimized shuttle cells. Intranasal administration (INA) was selected due to its non-invasive nature and the potential to bypass the blood-brain barrier (BBB). Our findings demonstrate that the INA of XVir-N-31-loaded shuttle cells successfully delivered OAVs to the core tumor and invasive GBM cells, significantly prolonged the survival of the GBM-bearing mice, induced immunogenic cell death and finally reduced the tumor burden, all this highlighting the therapeutic potential of this innovative approach. Overall, this study provides compelling evidence for the effectiveness of the INA of XVir-N-31 via shuttle cells as a promising therapeutic strategy for GBM. The non-invasive nature of the INA of OV-loaded shuttle cells holds great promise for future clinical translation. However, further research is required to assess the efficacy of this approach to ultimately progress in human clinical trials.