Frontiers in Molecular Biosciences (May 2023)

Construction of VSVΔ51M oncolytic virus expressing human interleukin-12

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

DOI
https://doi.org/10.3389/fmolb.2023.1190669
Journal volume & issue
Vol. 10

Abstract

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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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