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

Authors: HE, JINJIAO - Northeast Agricultural University; AN, YING - National Center For Agriculture And Forestry Technologies (CENTA); QI, JIANYING - Northeast Agricultural University; CUI, LIN - Northeast Agricultural University; YANG, KAI - Northeast Agricultural University; LIU, MINGYAO - Northeast Agricultural University; QU, BO - Northeast Agricultural University; YAN, SHIJUN - Northeast Agricultural University; YIN, JIECHAO - Northeast Agricultural University; JING, XIAOHUI - Northeast Agricultural University; DONG, HUI - Northeast Agricultural University; Yu, Qingzhong; LI, DESHAN - Northeast Agricultural University; WU, YUNZHOU - Northeast Agricultural University, China

Submitted to: Journal of Medical Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/4/2020
Publication Date: 8/11/2020
Citation: He, J., An, Y., Qi, J., Cui, L., Yang, K., Liu, M., Qu, B., Yan, S., Yin, J., Jing, X., Dong, H., Yu, Q., Li, D., Wu, Y. 2020. The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model. Journal of Medical Virology. 93(6):3890-3898. https://doi.org/10.1002/jmv.26419.
DOI: https://doi.org/10.1002/jmv.26419

Interpretive Summary: Newcastle disease virus (NDV) is an avian pathogen, and some strains of NDV can selectively lyse tumor cells. In this report, we developed a oncolytic NDV, Anhinga strain, as a vector to express human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for use as a cancer therapeutic agent. Administration of the NDV Anhinga/TRAIL recombinant virus in a mouse-model with tumor and in a tumor cell line (U251) inhibited tumor growth in mice and induced programed death of the tumor cells. These results suggest that the NDV Anhinga/TRAIL recombinant virus is a potential tumor therapeutic agent.

Technical 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'mm3), when compared with the NDV wild type (205.03'mm3, P'<'.05) and PBS (310.30'mm3, P'<'.01) groups.