Construction of VSVΔ51M oncolytic virus expressing human interleukin-12

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

doi:10.3389/fmolb.2023.1190669

Construction of VSVΔ51M oncolytic virus expressing human interleukin-12

Front Mol Biosci. 2023 May 15:10:1190669. doi: 10.3389/fmolb.2023.1190669. eCollection 2023.

Authors

Rwaa H Abdulal^{1

2}, Jana S Malki¹, Ezdehar Ghazal¹, Ahdab A Alsaieedi^{1

3}, Sarah A Almahboub¹, Muhammad Yasir Khan^{1

2}, Reem M Alsulaiman¹, Mazen M Ghaith⁴, Turki S Abujamel^{1

3}, Magdah Ganash², Ahmad Bakur Mahmoud^{5

6}, Almohanad A Alkayyal⁷, Anwar M Hashem^{1

8}

Affiliations

¹ Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Biological Science, Faculty of Science, King AbdulAziz University, Jeddah, Saudi Arabia.
³ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
⁵ College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia.
⁶ Strategic Research and Innovation Laboratories, Taibah University, Madinah, Saudi Arabia.
⁷ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
⁸ Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

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.

Keywords: B16F10; MCF-7; VSVΔ51M; cancer immunotherapy; interleukin-12; oncolytic virus.

Grants and funding

This research work was funded by the Institutional Fund Project under grant no (IFPRC-161-290-2020). Therefore, authors gratefully acknowledge technical and financial support from the Ministry of Education and King Abdulaziz University, Jeddah, Saudi Arabia.