Construction of VSVΔ51M oncolytic virus expressing human interleukin-12

表达人白细胞介素-12的VSVΔ51M溶瘤病毒的构建

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作者:Rwaa H Abdulal, Jana S Malki, Ezdehar Ghazal, Ahdab A Alsaieedi, Sarah A Almahboub, Muhammad Yasir Khan, Reem M Alsulaiman, Mazen M Ghaith, Turki S Abujamel, Magdah Ganash, Ahmad Bakur Mahmoud, Almohanad A Alkayyal, Anwar M Hashem

Abstract

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.

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