Oncolytic Newcastle disease virus carrying the IL24 gene exerts antitumor effects by inhibiting tumor growth and vascular sprouting

• Published in: International immunopharmacology Vol. 136; p. 112305
• Main Authors: Wu, Qing, Jin, Yuhan, Li, Shuang, Guo, Xiaochen, Sun, Wenying, Liu, Jinmiao, Li, Qianhui, Niu, Dun, Zou, Yimeng, Du, Xin, Li, Yanan, Zhao, Tianqi, Li, Zhitong, Li, Xinyu, Ren, Guiping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.07.2024
• Subjects: Animals; Antitumor; Apoptosis; Carcinoma, Hepatocellular - therapy; Cell Line, Tumor; Cell Proliferation; Dendritic Cells - immunology; GM-CSF; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; IL24; Interleukins - genetics; Interleukins - metabolism; Liver Neoplasms - therapy; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic - therapy; Newcastle disease virus - genetics; Newcastle disease virus - physiology; Oncolytic Virotherapy - methods; Oncolytic Viruses - genetics; Oncolytic Viruses - physiology; Recombinant Newcastle disease virus (NDV); T-Lymphocytes - immunology; Tumor-bearing mice; Tumor-bearing mice; GM-CSF; Recombinant Newcastle disease virus (NDV); IL24; Antitumor
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112305

[Display omitted] •In this study, we successfully constructed oncolytic NDV viruses carrying IL24 and GM-CSF genes using the genome of NDV rClone30 strain as a vector using reverse genetics.•In vitro experiments have shown that oncolytic NDV virus can successfully infect tumor cells and stably express exogenous proteins. The recombinant viruses exerted their antitumor effects by inhibiting tumor cell growth and migration and promoting tumor cell syncytium formation and apoptosis.•In vivo experiments showed that the oncolytic NDV virus prolonged the survival of tumor-bearing mice model by inhibiting tumor growth and inducing anti-tumor immune responses through the T cell and DC cell immune pathways. The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.