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Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma

  • Translational Research and Biomarkers
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Abstract

Background

Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery.

Methods

Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy.

Results

The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed.

Conclusions

VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.

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Acknowledgment

This work was funded by the Ken Bendix Memorial Grant of the Mesothelioma Applied Research Foundation, to J. Andrea McCart.

Conflict of interest

Dr. McCart is a co-inventor of the vvDD.

Author information

Authors and Affiliations

  1. Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, Toronto, ON, Canada

    Sergio A. Acuna MD, Kathryn Ottolino-Perry BSc, Besmira Çako BSc, Nan Tang MSc, Fernando A. Angarita MD & J. Andrea McCart MD, MSc, FRCS(C)

  2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Kathryn Ottolino-Perry BSc, Fernando A. Angarita MD & J. Andrea McCart MD, MSc, FRCS(C)

  3. Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada

    J. Andrea McCart MD, MSc, FRCS(C)

  4. Division of General Surgery, Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada

    J. Andrea McCart MD, MSc, FRCS(C)

Authors
  1. Sergio A. Acuna MD
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  2. Kathryn Ottolino-Perry BSc
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  3. Besmira Çako BSc
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  4. Nan Tang MSc
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  5. Fernando A. Angarita MD
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  6. J. Andrea McCart MD, MSc, FRCS(C)
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Corresponding author

Correspondence to J. Andrea McCart MD, MSc, FRCS(C).

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Acuna, S.A., Ottolino-Perry, K., Çako, B. et al. Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma. Ann Surg Oncol 21, 2259–2266 (2014). https://doi.org/10.1245/s10434-014-3651-4

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  • DOI: https://doi.org/10.1245/s10434-014-3651-4

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