Related Experiment Video
Updated: Jun 12, 2025
12:42
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
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IL-12-mediated toxicity from localized oncolytic virotherapy can be reduced using systemic TNF blockade
Miriam Valenzuela-Cardenas1, Carrie Fisher2, Mee Y Bartee1
1Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Molecular Therapy. Oncology
|September 18, 2024
Summary
Recombinant oncolytic viruses deliver cytokines for cancer therapy, but systemic toxicities persist. These toxicities, mediated by tumor necrosis factor α, can be reduced using FDA-approved tumor necrosis factor blockers.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Cancer treatment
Background:
- Cytokine therapy improves cancer outcomes but causes severe toxicities.
- Recombinant oncolytic viruses deliver cytokines to tumors, enhancing efficacy and reducing side effects.
- A vPD1/IL-12 myxoma virus effectively regresses disseminated cancers.
Purpose of the Study:
- To investigate the mechanisms of systemic toxicity associated with vPD1/IL-12.
- To identify strategies for mitigating these toxicities in cancer patients.
Main Methods:
- Treatment of disseminated cancers with a doubly recombinant oncolytic myxoma virus (vPD1/IL-12).
- Analysis of transgene biodistribution and systemic toxicity.
- Investigation of cytokine-mediated toxicity pathways, including interferon-γ and tumor necrosis factor α (TNF-α).
- Evaluation of TNF blockers for toxicity mitigation.
Main Results:
- vPD1/IL-12 treatment caused systemic toxicities despite localized transgene expression.
- Toxicities were independent of interferon-γ.
- Systemic toxicities were mediated by TNF-α interacting with TNF receptor 2 on hematopoietic cells.
- Etanercept, an FDA-approved TNF blocker, alleviated vPD1/IL-12-mediated toxicities.
Conclusions:
- Systemic IL-12 toxicity from oncolytic viruses can occur independently of interferon-γ.
- TNF-α and TNF receptor 2 mediate these toxicities in hematopoietic cells.
- TNF blockers offer a viable strategy to manage oncolytic virus-induced toxicities, improving clinical applicability.
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