AUTHOR=Abdulal Rwaa H. , Malki Jana S. , Ghazal Ezdehar , Alsaieedi Ahdab A. , Almahboub Sarah A. , Khan Muhammad Yasir , Alsulaiman Reem M. , Ghaith Mazen M. , Abujamel Turki S. , Ganash Magdah , Mahmoud Ahmad Bakur , Alkayyal Almohanad A. , Hashem Anwar M. TITLE=Construction of VSVΔ51M oncolytic virus expressing human interleukin-12 JOURNAL=Frontiers in Molecular Biosciences VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1190669 DOI=10.3389/fmolb.2023.1190669 ISSN=2296-889X 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.