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BMC Medicine
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Herpes Simplex Type 2 | Research article

SIRPα antibody combined with oncolytic virus OH2 protects against tumours by activating innate immunity and reprogramming the tumour immune microenvironment

Authors: Defeng Kong, Zhenrong Yang, Guoliang Li, Quanyou Wu, Zhaoru Gu, Duo Wan, Qi Zhang, Xiaoli Zhang, Shujun Cheng, Binlei Liu, Kaitai Zhang, Wen Zhang

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

The combination of oncolytic viruses (OVs) with immune checkpoint blockades is a research hotspot and has shown good efficacy. Here, we present the first attempt to combine oncolytic herpes simplex virus 2 (OH2) with an anti-SIRPα antibody as an antitumour treatment. Our results provide unique insight into the combination of innate immunity with OV.

Methods

We verified the polarization and activation of OH2 in RAW264.7 cells in vitro. Subsequently, we evaluated the antitumour ability of OH2 and anti-SIRPα combined therapy in a tumour-bearing mouse model. RNA-seq and Single-cell RNA-seq were used to characterize the changes in the tumour microenvironment.

Results

The OH2 lysates effectively stimulated RAW264.7 cells to polarize towards the M1 but not the M2 phenotype and activated the function of the M1 phenotype in vitro. In the macrophage clearance experiment, OH2 therapy induced polarization of M1 macrophages and participated in the antitumour immune response in a tumour-bearing mouse model. Treatment with a combination of OH2 and anti-SIRPα effectively inhibited tumour growth and significantly prolonged the survival time of the mice, and this result was more obvious in the mouse model with a larger tumour volume at the beginning of the treatment. These results suggest that combination therapy can more profoundly reshape the TME and activate stronger innate and adaptive immune responses.

Conclusions

Our data support the feasibility of oncolytic virus therapy in combination with anti-SIRPα antibodies and suggest a new strategy for oncolytic virus therapy.
Appendix
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Metadata
Title
SIRPα antibody combined with oncolytic virus OH2 protects against tumours by activating innate immunity and reprogramming the tumour immune microenvironment
Authors
Defeng Kong
Zhenrong Yang
Guoliang Li
Quanyou Wu
Zhaoru Gu
Duo Wan
Qi Zhang
Xiaoli Zhang
Shujun Cheng
Binlei Liu
Kaitai Zhang
Wen Zhang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02574-z

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