Unlocking oncolytic virotherapy potential: leveraging bacteriophages to conquer immunosuppression
- 1American School of Doha
- 2Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke
- 3Beckman Coulter Life Sciences
Abstract
Oncolytic virotherapy (OVT) offers great potential as an immunotherapy by lysing cancer cells and inducing immunogenic cell death, inciting an anti-tumor immune response. However, immunosuppressive tumor microenvironments (TMEs) in “cold” solid tumors limit OVT effectiveness by reducing viral infiltration and immune responses. Bacteriophages—safe, manipulable bacterial viruses—and their derived mechanisms are emerging as promising tools to address this gap by minimizing TME immunosuppression, maximizing anti-tumor immune activation, and improving overall precision and effectiveness. Bacteriophage characteristics such as their repetitive peptide presentation, biological barrier degradation, and superior payload delivery capabilities can be harnessed for OVT to improve therapy effectiveness. This review explores how engineered OVT can leverage such bacteriophage-derived components through two main approaches. The established synergistic approach allows chimeric vectors such as AAVP to integrate phage safety, cargo capabilities, and precision into OVT. The proposed modular approach aims to transfer specific desirable traits from phages to replication-capable OVs. For example, through novel AI and genetic engineering technology, the first mammalian encoded hyaluronate lyase can be synthetically created. The products of this traditionally prokaryotic enzyme avoid the tumor-progressing effects of current mammalian extracellular matrix-degrading hyaluronate lyases.
Related
- Targeting Toll-like Receptors to Enhance Oncolytic Virotherapy: Strategies and Emerging Perspectives
- Liver-resident cellular determinants of oncolytic virotherapy in hepatocellular carcinoma: viral susceptibility and spatial immune remodeling.
- Oncolytic reovirus: tumor-microenvironment remodeling, engineering constraints, and translational strategies
- Therapeutic potential of oncolytic viruses in hematopoietic malignancies: from preclinical insights to clinical realities
- Oncolytic measles virus reprograms the tumor microenvironment in a vascularized mesothelioma-on-chip model
BibTeX
@article{boulfrad2026unlocking,
title = {{Unlocking oncolytic virotherapy potential: leveraging bacteriophages to conquer immunosuppression}},
author = {Bilel Boulfrad and Anis Larbi},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1957551},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1957551/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unlocking oncolytic virotherapy potential: leveraging bacteriophages to conquer immunosuppression
AU - Bilel Boulfrad
AU - Anis Larbi
PY - 2026
DA - 2026/10/21
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1957551
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1957551/full
AB - Oncolytic virotherapy (OVT) offers great potential as an immunotherapy by lysing cancer cells and inducing immunogenic cell death, inciting an anti-tumor immune response. However, immunosuppressive tumor microenvironments (TMEs) in “cold” solid tumors limit OVT effectiveness by reducing viral infiltration and immune responses. Bacteriophages—safe, manipulable bacterial viruses—and their derived mechanisms are emerging as promising tools to address this gap by minimizing TME immunosuppression, maximizing anti-tumor immune activation, and improving overall precision and effectiveness. Bacteriophage characteristics such as their repetitive peptide presentation, biological barrier degradation, and superior payload delivery capabilities can be harnessed for OVT to improve therapy effectiveness. This review explores how engineered OVT can leverage such bacteriophage-derived components through two main approaches. The established synergistic approach allows chimeric vectors such as AAVP to integrate phage safety, cargo capabilities, and precision into OVT. The proposed modular approach aims to transfer specific desirable traits from phages to replication-capable OVs. For example, through novel AI and genetic engineering technology, the first mammalian encoded hyaluronate lyase can be synthetically created. The products of this traditionally prokaryotic enzyme avoid the tumor-progressing effects of current mammalian extracellular matrix-degrading hyaluronate lyases.
SN - 1664-302X
ER -