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

Nature communications | 2021

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.

Pubmed ID: 34625564 RIS Download

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI129582
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS106170
  • Agency: NCI NIH HHS, United States
    Id: R21 CA223400
  • Agency: NCI NIH HHS, United States
    Id: R00 CA201075
  • Agency: NCI NIH HHS, United States
    Id: R35 CA210087
  • Agency: NCI NIH HHS, United States
    Id: R01 CA255250
  • Agency: NCI NIH HHS, United States
    Id: U19 CA264512
  • Agency: NCI NIH HHS, United States
    Id: P30 CA033572
  • Agency: NCI NIH HHS, United States
    Id: P01 CA163205
  • Agency: NCI NIH HHS, United States
    Id: R01 CA247550
  • Agency: NCI NIH HHS, United States
    Id: R01 CA265095

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