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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Cancer Biology and Translational Studies

Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity

Sang-In Kim, Anthony K. Park, Shyambabu Chaurasiya, Seonah Kang, Jianming Lu, Annie Yang, Venkatesh Sivanandam, Zhifang Zhang, Yanghee Woo, Saul J. Priceman, Yuman Fong and Susanne G. Warner
Sang-In Kim
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Anthony K. Park
2Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Shyambabu Chaurasiya
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Seonah Kang
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Jianming Lu
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Annie Yang
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Venkatesh Sivanandam
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Zhifang Zhang
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Yanghee Woo
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
3Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, California.
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Saul J. Priceman
2Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
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Yuman Fong
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
3Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, California.
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Susanne G. Warner
1Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
3Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, California.
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  • ORCID record for Susanne G. Warner
  • For correspondence: suwarner@coh.org
DOI: 10.1158/1535-7163.MCT-20-0405 Published January 2021
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Abstract

Although it is known that oncolytic viruses can inflame and recruit immune cells to otherwise immunosuppressed tumor microenvironments, the influence of the antiviral immune response on antitumor immunity is less clear across viral platforms and tumor types. CF33 is a recombinant orthopoxvirus backbone effective against colon cancer. We tested derivatives of CF33 with and without immune-checkpoint inhibition (anti–PD-L1) in mouse models of colon cancer. Results showed that the efficacy of CF33 backbone with J2R deletion (single-deleted) against colon cancer is not altered by additional deletion of F14.5L in vitro or in vivo. CF33 infection upregulated PD-L1 expression on tumor cells and led to an increased influx of lymphocytes and macrophages in tumors. Also, the levels of active CD8+ (IFNγ+) T cells in the virus-treated tumors were higher than those in control-treated tumors. Furthermore, a combination of CF33 derivatives with anti–PD-L1 resulted in durable tumor regression and long-term survival, resistant to tumor rechallenge. Analysis of immune cells from the treated mice showed that tumor-specific T cell activation occurred more robustly in tumors treated with the virus and that T cells were more strongly activated against the virus than against tumor, in an MHC-I–dependent manner. Our findings warrant further studies on the role of cross-priming of T cells against viral and tumor antigens, in the overall success of viroimmunotherapy.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Mol Cancer Ther 2021;20:173–82

  • Received May 13, 2020.
  • Revision received August 4, 2020.
  • Accepted October 8, 2020.
  • Published first December 1, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 20 (1)
January 2021
Volume 20, Issue 1
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Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity
Sang-In Kim, Anthony K. Park, Shyambabu Chaurasiya, Seonah Kang, Jianming Lu, Annie Yang, Venkatesh Sivanandam, Zhifang Zhang, Yanghee Woo, Saul J. Priceman, Yuman Fong and Susanne G. Warner
Mol Cancer Ther January 1 2021 (20) (1) 173-182; DOI: 10.1158/1535-7163.MCT-20-0405

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Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity
Sang-In Kim, Anthony K. Park, Shyambabu Chaurasiya, Seonah Kang, Jianming Lu, Annie Yang, Venkatesh Sivanandam, Zhifang Zhang, Yanghee Woo, Saul J. Priceman, Yuman Fong and Susanne G. Warner
Mol Cancer Ther January 1 2021 (20) (1) 173-182; DOI: 10.1158/1535-7163.MCT-20-0405
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Molecular Cancer Therapeutics
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