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.
胶质母细胞瘤（GBM）是一种侵袭性强、致死率高的原发性脑肿瘤，治疗手段有限且预后极差。溶瘤病毒疗法（OVT）已成为一种有前景的GBM治疗策略。然而，当溶瘤病毒（OV）通过瘤内注射给药时，肿瘤周围非肿瘤细胞可能阻碍其到达侵袭性GBM细胞。本研究利用两种异种移植GBM小鼠模型及免疫荧光分析技术，探讨了通过负载病毒的优化载体细胞经鼻递送溶瘤腺病毒（OAV）XVir-N-31的效果。选择鼻内给药（INA）方式是基于其无创特性及可能突破血脑屏障（BBB）的优势。研究结果表明：负载XVir-N-31的载体细胞经鼻给药能成功将OAV递送至核心肿瘤及侵袭性GBM细胞，显著延长荷瘤小鼠生存期，诱导免疫原性细胞死亡，最终降低肿瘤负荷，充分彰显了这一创新疗法的治疗潜力。总体而言，本研究为经载体细胞鼻内递送XVir-N-31作为GBM治疗策略的有效性提供了有力证据。负载OV的载体细胞经鼻给药的无创特性为未来临床转化带来巨大希望，但仍需进一步研究评估该方法的疗效，以推动其最终进入人体临床试验阶段。
肿瘤(癌症)患者之家