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

Tolulope O Omolekan1, Joy T Folahan1, Mulu Z Tesfay2,3

  • 1Department of Pathological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.

Frontiers in Immunology
|September 10, 2025
PubMed

Insights

Oncolytic virotherapy (OVT) uses engineered viruses to destroy cancer cells. Advances in virus engineering and combination therapies are improving OVT efficacy for precision oncology.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Oncolytic virotherapy (OVT) is a cancer treatment using engineered viruses to selectively kill malignant cells.
  • Oncolytic viruses (OVs) also modulate the tumor microenvironment (TME) and stimulate antitumor immunity.
  • Current OVT faces challenges like poor virus delivery, immune clearance, and tumor heterogeneity.

Purpose of the Study:

  • To review innovations in next-generation OV engineering.
  • To explore emerging combination strategies for OVT.
  • To discuss future directions for overcoming OVT resistance and maximizing clinical efficacy.

Main Methods:

  • Review of recent advances in OV engineering, including enhanced tropism, immune evasion, and transgene delivery.
  • Analysis of combination strategies involving OVs with immune checkpoint inhibitors (ICIs), chemotherapeutics, and immunometabolic modulators.
  • Discussion of mechanistic insights into OV function and TME modulation.

Main Results:

  • Engineered OVs show improved tumor targeting, penetration, and sustained immune activation.
  • Combination strategies are transforming OVT into a versatile precision oncology approach.
  • Advances address key barriers limiting OVT's therapeutic potential.

Conclusions:

  • Next-generation OV engineering enhances oncolytic and immunotherapeutic properties.
  • Combination therapies are crucial for maximizing OVT efficacy and overcoming resistance.
  • Future research should focus on optimizing OV delivery and combination strategies for improved clinical outcomes.
Keywords:
cancer immunotherapycancer therapycombination therapyengineered virusesimmune evasiononcolytic virusespharmacological treatmenttumor targeting

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