SIRPα 抗体与溶瘤病毒 OH2 联合通过激活先天免疫和重编程肿瘤免疫微环境来抵抗肿瘤。

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

机构信息

State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, 430068, China.

出版信息

BMC Med. 2022 Oct 31;20(1):376. doi: 10.1186/s12916-022-02574-z.

DOI:10.1186/s12916-022-02574-z

PMID:36310169

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9620659/

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.

摘要

背景

溶瘤病毒（OVs）与免疫检查点阻断的联合是一个研究热点，已显示出良好的疗效。在这里，我们首次尝试将单纯疱疹病毒 2 型溶瘤病毒（OH2）与抗 SIRPα 抗体联合用于抗肿瘤治疗。我们的研究结果为固有免疫与 OV 的联合提供了独特的见解。

方法

我们在 RAW264.7 细胞中验证了 OH2 的极化和激活。随后，我们在荷瘤小鼠模型中评估了 OH2 和抗 SIRPα联合治疗的抗肿瘤能力。RNA-seq 和单细胞 RNA-seq 用于表征肿瘤微环境的变化。

结果

OH2 裂解物有效地刺激 RAW264.7 细胞向 M1 极化，而不是 M2 表型，并在体外激活 M1 表型的功能。在巨噬细胞清除实验中，OH2 治疗诱导 M1 巨噬细胞极化，并在荷瘤小鼠模型中参与抗肿瘤免疫反应。OH2 和抗 SIRPα联合治疗可有效抑制肿瘤生长，显著延长小鼠的生存时间，而在开始治疗时肿瘤体积较大的小鼠模型中，这一效果更为明显。这些结果表明，联合治疗可以更深刻地重塑 TME，并激活更强的固有和适应性免疫反应。