Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses

Authors

• Tolulope O. Omolekan, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Joy T. Folahan, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Mulu Z. Tesfay, University of Arkansas for Medical Sciences, Little Rock, AR
• Harikrishnan Mohan, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Ojasvi Dutta, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Leila Rahimian, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Khandoker Usran Ferdous, University of Arkansas for Medical Sciences, Little Rock, AR
• Reza Ghavimi, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Aleksandra Cios, University of Maryland School of Medicine, Baltimore, MD
• Timothy K. Beng, Central Washington University, Ellensburg, WA
• Joseph Francis, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Oswald D'Auvergne, Southern University and A&M College, Baton Rouge, LA
• Mitesh J. Borad, Mayo Clinic, Rochester, MN
• Konstantin G. Kousoulas, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Stephen DiGiuseppe, Edward Via College of Osteopathic Medicine, Monroe, LA
• Bolni Marius Nagalo, University of Maryland School of Medicine, Baltimore, MD
• Jean Christopher Chamcheu, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA

Document Type

Article

Publication Date

8-24-2025

Publication Title

Frontiers in Immunology

Abstract

Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and tumor heterogeneity, continue to limit the therapeutic advantages of OVT as a standalone modality and hindered its clinical success. Recent advances in OV engineering have enhanced viral tropism, immune evasion, and transgene delivery, enabling better tumor targeting and penetration and sustained immune activation in malignant tumors. Moreover, rational combination strategies with immune checkpoint inhibitors (ICIs), chemotherapeutics, and immunometabolic modulators are reshaping OVT into a versatile strategy for precision oncology. This review highlights the mechanistic innovations driving next-generation OV engineering, explores emerging combination regimens, and discusses future directions to overcome resistance and maximize clinical efficacy.

First Page

1

Last Page

34

DOI

10.3389/fimmu.2025.1618751

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Omolekan, Tolulope O.; Folahan, Joy T.; Tesfay, Mulu Z.; Mohan, Harikrishnan; Dutta, Ojasvi; Rahimian, Leila; Ferdous, Khandoker Usran; Ghavimi, Reza; Cios, Aleksandra; Beng, Timothy K.; Francis, Joseph; D'Auvergne, Oswald; Borad, Mitesh J.; Kousoulas, Konstantin G.; DiGiuseppe, Stephen; Nagalo, Bolni Marius; and Chamcheu, Jean Christopher, "Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses" (2025). LSU-LCMC Cancer Center Faculty Publications. 220.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/220
10.3389/fimmu.2025.1618751