The development of new tools against glioblastoma multiforme (GBM), the most aggressive and common cancer originating in the brain, remains of utmost importance. Lentiviral vectors (LVs) are among the tools of future concepts, and pseudotyping offers the possibility of tailoring LVs to efficiently transduce and inactivate GBM tumor cells. Zika virus (ZIKV) has a specificity for GBM cells, leaving healthy brain cells unharmed, which makes it a prime candidate for the development of LVs with a ZIKV coat. Here, primary GBM cell cultures were transduced with different LVs encased with ZIKV envelope variants. LVs were generated by using the pNLgfpAM plasmid, which produces the lentiviral, HIV-1-based, core particle with GFP (green fluorescent protein) as a reporter (HIVgfp). Using five different GBM primary cell cultures and three laboratory-adapted GBM cell lines, we showed that ZIKV/HIVgfpachieved a 4–6 times higher transduction efficiency compared to the commonly used VSV/HIVgfp. Transduced GBM cell cultures were monitored over a period of 9 days to identify GFP+ cells to study the oncolytic effect due to ZIKV/HIVgfpentry. Tests of GBM tumor specificity by transduction of GBM tumor and normal brain cells showed a high specificity for GBM cells.
针对胶质母细胞瘤（GBM）这一最具侵袭性且最常见的脑源性癌症，开发新型治疗工具仍至关重要。慢病毒载体（LVs）是未来治疗方案的重要工具之一，而假型化技术能够定制慢病毒载体，从而有效转导并灭活GBM肿瘤细胞。寨卡病毒（ZIKV）对GBM细胞具有特异性靶向能力，且不损伤健康脑细胞，这使其成为开发ZIKV包膜慢病毒载体的理想候选。本研究采用不同ZIKV包膜变体包裹的慢病毒载体转导原代GBM细胞培养物。慢病毒载体通过pNLgfpAM质粒构建，该质粒可产生以绿色荧光蛋白（GFP）为报告基因、基于HIV-1的慢病毒核心颗粒（HIVgfp）。通过五种不同的原代GBM细胞培养物和三种实验室适应型GBM细胞系实验，我们发现ZIKV/HIVgfp的转导效率较常用的VSV/HIVgfp提高4-6倍。对转导后的GBM细胞培养物进行为期9天的监测，通过识别GFP阳性细胞研究ZIKV/HIVgfp进入细胞后产生的溶瘤效应。通过对比转导GBM肿瘤细胞与正常脑细胞的实验，证实该载体对GBM细胞具有高度特异性。
肿瘤(癌症)患者之家