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An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

Author

Listed:
  • Bo Xu

    (City of Hope National Medical Center)

  • Lei Tian

    (City of Hope National Medical Center)

  • Jing Chen

    (City of Hope Comprehensive Cancer Centre)

  • Jing Wang

    (City of Hope National Medical Center)

  • Rui Ma

    (City of Hope National Medical Center)

  • Wenjuan Dong

    (City of Hope National Medical Center)

  • Aimin Li

    (City of Hope National Medical Center)

  • Jianying Zhang

    (City of Hope National Medical Center)

  • E. Antonio Chiocca

    (Brigham and Women’s Hospital and Harvey Cushing Neuro-oncology Laboratories, Harvard Medical School)

  • Balveen Kaur

    (University of Texas, University of Texas Health Science Center at Houston)

  • Mingye Feng

    (City of Hope Comprehensive Cancer Centre)

  • Michael A. Caligiuri

    (City of Hope National Medical Center
    Comprenhensive Cancer Center, City of Hope
    City of Hope National Medical Center)

  • Jianhua Yu

    (City of Hope National Medical Center
    City of Hope Comprehensive Cancer Centre
    Comprenhensive Cancer Center, City of Hope
    City of Hope National Medical Center)

Abstract

Oncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 ‘don’t eat me’ signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.

Suggested Citation

  • Bo Xu & Lei Tian & Jing Chen & Jing Wang & Rui Ma & Wenjuan Dong & Aimin Li & Jianying Zhang & E. Antonio Chiocca & Balveen Kaur & Mingye Feng & Michael A. Caligiuri & Jianhua Yu, 2021. "An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26003-6
    DOI: 10.1038/s41467-021-26003-6
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    Cited by:

    1. Shiqun Wang & Wei Yan & Lingkai Kong & Shuguang Zuo & Jingyi Wu & Chunxiao Zhu & Huaping Huang & Bohao He & Jie Dong & Jiwu Wei, 2023. "Oncolytic viruses engineered to enforce cholesterol efflux restore tumor-associated macrophage phagocytosis and anti-tumor immunity in glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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