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Updated: Dec 13, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Collateral Lethal Effects of Complementary Oncolytic Viruses
Justin W Maroun1,2, Velia Penza1, Taylor M Weiskittel1,2
1Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Abstract:
Virus-infected cells release type 1 interferons, which induce an antiviral state in neighboring cells. Naturally occurring viruses are therefore equipped with stealth replication strategies to limit virus sensing and/or with combat strategies to prevent or reverse the antiviral state. Here we show that oncolytic viruses with simple RNA genomes whose spread was suppressed in tumor cells pretreated with interferon were able to replicate efficiently when the cells were coinfected with a poxvirus known to encode a diversity of innate immune combat proteins. In vivo the poxvirus was shown to reverse the intratumoral antiviral state, rescuing RNA virus replication in an otherwise restrictive syngeneic mouse tumor model leading to antitumor efficacy. Pairing of complementary oncolytic viruses is a promising strategy to enhance the antitumor activity of this novel class of anticancer drugs.
Insights
Oncolytic viruses can be enhanced by pairing them with poxviruses. This combination overcomes the antiviral state in tumors, improving cancer treatment efficacy and promoting virus replication.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Virus-infected cells release type 1 interferons, inducing an antiviral state in neighboring cells.
- Viruses employ stealth or combat strategies to evade or counteract host antiviral responses.
- Oncolytic viruses are a novel class of anticancer drugs.
Purpose of the Study:
- To investigate if coinfection with poxviruses can enhance the replication and antitumor efficacy of oncolytic RNA viruses.
- To determine if poxviruses can reverse the interferon-induced antiviral state in tumor cells.
Main Methods:
- Tumor cells pretreated with interferon were coinfected with oncolytic RNA viruses and a poxvirus.
- Viral replication was assessed in vitro.
- Antitumor efficacy was evaluated in a syngeneic mouse tumor model in vivo.
Main Results:
- Oncolytic RNA viruses replicated efficiently when coinfected with poxviruses, despite interferon pretreatment.
- The poxvirus reversed the intratumoral antiviral state in vivo.
- This rescue of RNA virus replication led to significant antitumor efficacy.
Conclusions:
- Pairing oncolytic viruses with poxviruses is a promising strategy to enhance their antitumor activity.
- Poxviruses can overcome the host antiviral response, enabling effective oncolytic virotherapy.
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