Abstract：
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.
摘要：
第二大死因,癌症,对人类生命构成重大威胁。由于传统方法的局限性，癌症疗法的创新至关重要。新城疫病毒（NDV），一种非致病性溶瘤病毒，通过选择性感染表现出多功能的抗癌特性，复制,并消除肿瘤细胞.为了增强NDV的抗肿瘤活性，开发了四种溶瘤NDV病毒，使用反向遗传学在不同基因位点整合IL24和/或GM-CSF基因。体外实验表明，溶瘤NDV病毒增强了亲本病毒rClone30的抗肿瘤功效，抑制了肿瘤细胞的增殖，诱导肿瘤细胞融合，促进细胞凋亡。此外，携带IL24基因的NDV在CAM实验中抑制微血管形成。在肝癌小鼠模型中的评估证实了溶瘤NDV病毒疗法的治疗功效。用溶瘤NDV病毒治疗的小鼠的肿瘤大小显着减小，病理切片中伴有明显的肿瘤细胞脱离和凋亡。此外，溶瘤NDV病毒增强了T细胞和树突状细胞的产生，并大大提高了肝癌小鼠的生存率，rClone30-IL24（P/M）显示出显著的治疗效果。本研究为在临床实践中利用溶瘤NDV病毒作为抗肿瘤剂奠定了基础。
