Construction of VSVΔ51M oncolytic virus expressing human interleukin-12
Rwaa H. Abdulal, Jana S. Malki, Ezdehar Abdulraouf Ghazal, Ahdab 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.