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

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

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish (US)
Article number5908
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

Fingerprint

Dive into the research topics of 'An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma'. Together they form a unique fingerprint.

Cite this