The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model. Issue 6 (28th September 2020)

• Record Type: Journal Article
• Authors: He, Jinjiao; An, Ying; Qi, Jianying; Cui, Lin; Yang, Kai; Liu, Mingyao; Qu, Bo; Yan, Shijun; Yin, Jiechao; Jing, Xiaohui; Dong, Hui; Yu, Qingzhong; Li, Deshan; Wu, Yunzhou
• Is Part Of: Journal of medical virology. Volume 93:Issue 6(2021)
• Page Start: 3890
• Page End: 3898
• Publication Date: 2020-09-28
• Subjects: newcastle disease virus -- oncolytic -- TRAIL -- U251 glioma cell; Virology -- Periodicals; 616
• DOI: 10.1002/jmv.26419
• Languages: English
• ISSNs: 0146-6615

Abstract

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. Highlights: NDV/Anh‐TRAIL exerts an obvious result in U251 glioma therapeutic effect in vitro and in vivo. Anhinga strain could be an effectual vector for tumor therapy. NDV/Anh‐TRAIL could become a potent candidate for clinical treatment especially for glioma.