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Updated: May 25, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
ORFV: a novel oncolytic and immune stimulating parapoxvirus therapeutic
Julia L Rintoul1, Chantal G Lemay, Lee-Hwa Tai
1Department of Biochemistry, Microbiology & Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
Abstract:
Replicating viruses for the treatment of cancer have a number of advantages over traditional therapeutic modalities. They are highly targeted, self-amplifying, and have the added potential to act as both gene-therapy delivery vehicles and oncolytic agents. Parapoxvirus ovis or Orf virus (ORFV) is the prototypic species of the Parapoxvirus genus, causing a benign disease in its natural ungulate host. ORFV possesses a number of unique properties that make it an ideal viral backbone for the development of a cancer therapeutic: it is safe in humans, has the ability to cause repeat infections even in the presence of antibody, and it induces a potent T(h)-1-dominated immune response. Here, we show that live replicating ORFV induces an antitumor immune response in multiple syngeneic mouse models of cancer that is mediated largely by the potent activation of both cytokine-secreting, and tumoricidal natural killer (NK) cells. We have also highlighted the clinical potential of the virus by demonstration of human cancer cell oncolysis including efficacy in an A549 xenograft model of cancer.
Insights
Orf virus (ORFV) shows promise as a cancer therapy. This replicating virus activates anti-tumor immune cells, like natural killer (NK) cells, and demonstrates oncolytic potential in preclinical models.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Replicating viruses offer targeted, self-amplifying cancer treatment advantages.
- Orf virus (ORFV) is a safe, immunogenic parapoxvirus suitable for therapeutic development.
- ORFV induces a T(h)-1 immune response and can overcome pre-existing antibodies.
Purpose of the Study:
- To evaluate the potential of live replicating Orf virus (ORFV) as an oncolytic cancer therapeutic.
- To investigate the immune mechanisms underlying ORFV-mediated anti-tumor activity.
- To assess the efficacy of ORFV in preclinical cancer models.
Main Methods:
- Utilized multiple syngeneic mouse cancer models.
- Administered live replicating Orf virus (ORFV).
- Assessed immune cell activation (cytokine-secreting and tumoricidal natural killer [NK] cells) and tumor response.
- Demonstrated human cancer cell oncolysis and xenograft model efficacy.
Main Results:
- Live replicating ORFV induced significant anti-tumor immune responses in vivo.
- The anti-tumor effect was largely mediated by potent activation of cytokine-secreting and tumoricidal NK cells.
- ORFV demonstrated oncolysis of human cancer cells and efficacy in an A549 xenograft model.
Conclusions:
- Live replicating Orf virus (ORFV) effectively stimulates anti-tumor immunity.
- ORFV shows significant potential as a novel oncolytic viral therapy for cancer.
- The virus's ability to activate NK cells and its oncolytic properties warrant further clinical investigation.
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