DataSheet1_Construction of VSVΔ51M oncolytic virus expressing human interleukin-12.PDF

The use of oncolytic viruses (OVs) in combination with cytokines, such as IL-12, is a promising approach for cancer treatment that addresses the limitations of current standard treatments and traditional cancer immunotherapies. IL-12, a proinflammatory cytokine, triggers intracellular signaling pathways that lead to increased apoptosis of tumor cells and enhanced antitumor activity of immune cells via IFN-γ induction, making this cytokine a promising candidate for cancer therapy. Targeted expression of IL-12 within tumors has been shown to play a crucial role in tumor eradication. The recent development of oncolytic viruses enables targeted delivery and expression of IL-12 at the tumor site, thereby addressing the systemic toxicities associated with traditional cancer therapy. In this study, we constructed an oncolytic virus, VSVΔ51M, based on the commercially available VSV wild-type backbone and further modified it to express human IL-12. Our preclinical data confirmed the safety and limited toxicity of the modified virus, VSV-Δ51M-hIL-12, supporting its potential use for clinical development.

溶瘤病毒（oncolytic viruses，OVs）与白细胞介素12（IL-12）等细胞因子联合应用，是一种极具潜力的癌症治疗策略，可弥补当前标准疗法与传统癌症免疫疗法的固有局限。白细胞介素12作为促炎细胞因子，可触发细胞内信号通路，通过诱导干扰素-γ（IFN-γ）促进肿瘤细胞凋亡并增强免疫细胞的抗肿瘤活性，使其成为癌症治疗的极具潜力的候选分子。已有研究证实，白细胞介素12在肿瘤部位的靶向表达对肿瘤根除具有关键作用。近年来溶瘤病毒技术的进步，实现了白细胞介素12在肿瘤部位的靶向递送与表达，由此规避了传统癌症疗法所带来的全身毒性问题。本研究基于商业化野生型水泡性口炎病毒（VSV）骨架构建了溶瘤病毒VSVΔ51M，并对其进行基因改造以表达人源白细胞介素12（hIL-12）。本研究的临床前实验数据证实，改造后的病毒VSV-Δ51M-hIL-12具备良好安全性与可控毒性，为其后续临床开发提供了坚实支撑。