Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory

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Updated: Jun 26, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

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Naziia Kurmasheva1, Aida Said2,3, Boaz Wong2,4

  • 1Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Nature Communications
|May 15, 2024
PubMed

Insights

4-octyl itaconate enhances oncolytic virotherapy by suppressing antiviral immunity in cancer cells. This combination therapy improves outcomes in resistant tumors, offering a new strategy against cancer.

Area of Science:

  • Oncology
  • Immunology
  • Metabolomics

Background:

  • Oncolytic virotherapy faces challenges due to treatment resistance, often caused by inhibited viral spread within tumors.
  • Developing strategies to overcome resistance is crucial for improving the efficacy of oncolytic virotherapy.

Purpose of the Study:

  • To investigate the potential of 4-octyl itaconate (4-OI), a novel metabolite derivative, to enhance oncolytic virotherapy.
  • To elucidate the mechanisms by which 4-OI affects antiviral responses in cancer cells.

Main Methods:

  • Tested 4-OI in combination with VSVΔ51 (vesicular stomatitis virus) in various cancer models, including cell lines, 3D tumoroids, and organotypic slices.
  • Investigated the molecular mechanisms of 4-OI action, focusing on its effects on MAVS and IKKβ, and antiviral signaling pathways.

Main Results:

  • 4-octyl itaconate significantly enhanced the efficacy of VSVΔ51 in multiple resistant cancer models.
  • 4-OI was found to suppress antiviral immunity in cancer cells by modifying MAVS and IKKβ, independent of the NRF2/KEAP1 pathway.
  • Combination therapy improved therapeutic outcomes in a resistant murine colon tumor model.

Conclusions:

  • 4-octyl itaconate is a promising agent for enhancing oncolytic virotherapy against resistant cancers.
  • Combining metabolite-derived drugs with oncolytic viruses can overcome treatment resistance by interfering with type I IFN and NF-κB antiviral responses.

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