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Research Article

NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

Almohanad A. Alkayyal, Lee-Hwa Tai, Michael A. Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A. Ananth, Ahmad Bakur Mahmoud, Andrew P. Makrigiannis, Greg O. Cron, Blair Macdonald, E. Celia Marginean, David F. Stojdl, John C. Bell and Rebecca C. Auer
Almohanad A. Alkayyal
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.Department of Laboratory Medicine, University of Tabuk, Tabuk, Saudi Arabia.Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
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Lee-Hwa Tai
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
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Michael A. Kennedy
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
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Christiano Tanese de Souza
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
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Jiqing Zhang
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
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Charles Lefebvre
Apoptosis Research Centre, CHEO Research Institute, Ottawa, Ontario, Canada.
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Shalini Sahi
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
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Abhirami A. Ananth
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
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Ahmad Bakur Mahmoud
Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.Department of Medical Technology, Taibah University, Medina, Saudi Arabia.
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Andrew P. Makrigiannis
Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
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Greg O. Cron
Department of Medical Imaging, University of Ottawa, Ottawa, Ontario, Canada.Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada.
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Blair Macdonald
Department of Medical Imaging, University of Ottawa, Ottawa, Ontario, Canada.
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E. Celia Marginean
Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.
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David F. Stojdl
Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.Apoptosis Research Centre, CHEO Research Institute, Ottawa, Ontario, Canada.
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John C. Bell
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
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Rebecca C. Auer
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.
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  • For correspondence: rauer@toh.ca
DOI: 10.1158/2326-6066.CIR-16-0162
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Abstract

Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 1–11. ©2017 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Received July 20, 2016.
  • Revision received December 9, 2016.
  • Accepted January 11, 2017.
  • ©2017 American Association for Cancer Research.
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Published OnlineFirst February 16, 2017
doi: 10.1158/2326-6066.CIR-16-0162

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NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine
Almohanad A. Alkayyal, Lee-Hwa Tai, Michael A. Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A. Ananth, Ahmad Bakur Mahmoud, Andrew P. Makrigiannis, Greg O. Cron, Blair Macdonald, E. Celia Marginean, David F. Stojdl, John C. Bell and Rebecca C. Auer
Cancer Immunol Res February 16 2017 DOI: 10.1158/2326-6066.CIR-16-0162

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NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine
Almohanad A. Alkayyal, Lee-Hwa Tai, Michael A. Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A. Ananth, Ahmad Bakur Mahmoud, Andrew P. Makrigiannis, Greg O. Cron, Blair Macdonald, E. Celia Marginean, David F. Stojdl, John C. Bell and Rebecca C. Auer
Cancer Immunol Res February 16 2017 DOI: 10.1158/2326-6066.CIR-16-0162
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