Jia Xinyuan, Wang Lizheng, Feng Xinyao, Liu Wenmo, Wang Xupu, Li Fangshen, Liu Xinyao, Yu Jiahao, Yu Bin, Yu Xianghui
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Nano Lett. 2023 Dec 13;23(23):11120-11128. doi: 10.1021/acs.nanolett.3c03516. Epub 2023 Nov 30.
An oncolytic virus is a promising strategy for glioblastoma (GBM) therapy. However, there are still some challenges such as the blood-brain barrier (BBB) and preexisting immunity for targeted treatment of GBM with an oncolytic virus. In this study, two kinds of cell membrane-coated oncolytic adenoviruses (NCM-Ad and GCM-Ad) were prepared using neural stem cells (NSCs) and GBM cells as sources of membranes, respectively, and were shown to improve the targeted infectivity on GBM cells and avoid the immune clearance of preexisting neutralizing antibodies and . Specifically, NCM-Ad showed a strong ability to cross the BBB and target tumor cells . To improve the cytotoxicity to GBM, a capsid dual-modified oncolytic adenovirus (A4/k37) was also encapsulated, and NCM-A4/k37 showed outstanding tumor targeting and inhibition capacity in an orthotopic xenograft tumor model of GBM upon intravenous administration. This study provides a promising oncolytic virus-based targeted therapeutic strategy for glioma.
溶瘤病毒是胶质母细胞瘤（GBM）治疗的一种有前景的策略。然而，在用溶瘤病毒靶向治疗GBM时，仍存在一些挑战，如血脑屏障（BBB）和预先存在的免疫。在本研究中，分别使用神经干细胞（NSCs）和GBM细胞作为膜来源制备了两种细胞膜包被的溶瘤腺病毒（NCM-Ad和GCM-Ad），结果表明它们可提高对GBM细胞的靶向感染性，并避免预先存在的中和抗体的免疫清除。具体而言，NCM-Ad显示出强大的穿越血脑屏障并靶向肿瘤细胞的能力。为提高对GBM的细胞毒性，还封装了一种衣壳双修饰的溶瘤腺病毒（A4/k37），静脉注射后，NCM-A4/k37在GBM原位异种移植肿瘤模型中显示出出色的肿瘤靶向和抑制能力。本研究为胶质瘤提供了一种基于溶瘤病毒的有前景的靶向治疗策略。
