The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model

溶瘤病毒 病毒 新城疫 胶质瘤 病毒学 重组DNA 细胞凋亡 细胞毒性T细胞 重组病毒 肿瘤坏死因子α 生物 免疫学 医学 癌症研究 体外 生物化学 基因
作者
Jinjiao He,Ying An,Jianying Qi,Lin Cui,Kai S. Yang,Mingyao Liu,Bo Qu,Shijun Yan,Jiechao Yin,Xiaohui Jing,Hui Dong,Qingzhong Yu,Deshan Li,Yunzhou Wu
出处
期刊:Journal of Medical Virology [Wiley]
卷期号:93 (6): 3890-3898 被引量:14
标识
DOI:10.1002/jmv.26419
摘要

Abstract Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. However, the potential oncolytic ability of the recombinant newcastle disease virus (NDV) Anhinga strain carried with tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) has not been fully explored at present. In the present study, the recombinant NDV/Anh‐TRAIL that secretes soluble TRAIL was constructed and the experiment results suggested NDV/Anh‐TRAIL as a promising candidate for glioma therapy. Growth kinetic and TRAIL secreted quantity of recombinant NDV/Anh‐TRAIL virus were measured. Cytotoxic and cell apoptosis were analyzed for its anti‐glioma therapy in vitro. Nude mice were used for the in vivo evaluation. Both tumor volume and mice behavior after injection were observed. The recombinant virus replicated with the same kinetics as the parental virus and the highest expression of TRAIL (77.8 ng/L) was found at 48 hours. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, a tetrazole and flow cytometry data revealed that the recombinant NDV/Anh‐TRAIL (56.1 ± 8.2%) virus could induce a more severe apoptosis rate, when compared with the NDV wild type (37.2 ± 7.0%) and mock (7.0 ± 1.8%) groups ( P < .01), in U251 cells. Furthermore, in the present animal study, the average tumor volume was smaller in the NDV/Anh‐TRAIL group (97.21 mm 3 ), when compared with the NDV wild type (205.03 mm 3 , P < .05) and PBS (310.30 mm 3 , P < .01) groups.
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