Preclinical Safety Evaluation of Oncolytic Herpes Simplex Virus Type 2

Wang, Yang; Zhou, Xiaobing; Wu, Zhen; Hu, Han Hwa; Jin, Jing; Hu, Yanping; Dong, Yu-Ting; Zou, Jianwen; Mao, Zeyong; Shi, Xiaotai; Lyu, Jianjun; Fang, Zhizheng; Zhang, Wen; Zhu, Yujie; Li, Bo; Liu, Binlei

doi:10.1089/hum.2018.170

Cited by 18 publications

(6 citation statements)

References 18 publications

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“…OH2 was provided by Binhui Biopharmaceutical Co., Ltd. (Wuhan, China). The virus was an attenuated OH2 derived from the wild-type HSV-2 strain HG52 deleted the ICP47 gene and ICP34.5 gene [ 18 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

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

Kong

Yang

et al. 2022

BMC Med

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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.

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Section: Methodsmentioning

confidence: 99%

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

Kong

Yang

et al. 2022

BMC Med

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“…The second approach involves attenuating the pathogenicity of oncolytic viruses to normal cells by genetic modification of the viruses, many of which have been used in studies. To develop oncolytic HSV-1 drugs, such as T-VEC and G207, the ICP-34.5 gene in HSV1716, which is a neurovirulence factor of HSV, was deleted, attenuating the infectivity of HSV in normal neurons (73,117,122,124,125). Mutation and deletion of the E1 gene can reduce adenovirus selectivity of normal cells, and this genetic modification was made to the Onyx-015 and H10 viruses (90,126).…”

Section: Methods To Improve the Biosafety Of Oncolytic Virotherapymentioning

confidence: 99%

“…Clinical trials of oncolytic viruses such as G207, HSV1716, NV1020, Ad [I/PPT-E1A] and reovirus have proven their biosafety and effectiveness in tumor therapy (44,73,80,106,125). The HSV-2 and measles viruses were also proven non-toxic to humans in a number of mammalian experiments (124,(133)(134)(135). However, oncolytic virotherapies have unpredictability problems, such as long-term adverse events, which still need to be closely observed.…”

Section: Methods To Improve the Biosafety Of Oncolytic Virotherapymentioning

confidence: 99%

Delivery and Biosafety of Oncolytic Virotherapy

et al. 2020

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In recent years, oncolytic virotherapy has emerged as a promising anticancer therapy. Oncolytic viruses destroy cancer cells, without damaging normal tissues, through virus self-replication and antitumor immunity responses, showing great potential for cancer treatment. However, the clinical guidelines for administering oncolytic virotherapy remain unclear. Delivery routes for oncolytic virotherapy to patients vary in existing studies, depending on the tumor sites and the objective of studies. Moreover, the biosafety of oncolytic virotherapy, including mainly uncontrolled adverse events and long-term complications, remains a serious concern that needs to be accurately measured. This review provides a comprehensive and detailed overview of the delivery and biosafety of oncolytic virotherapy.

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“…Approximately 16.3% of patients treated with T-vec showed a lasting treatment response over 6 months, compared to only 2.1% of patients treated with control therapy [54] . A recombinant human GM-CSF oncolytic HSV-2 injection, named OH2, has the same modification strategy as T-vec [55] . The product OH2 has been approved by FDA for clinical trial for the treatment of advanced solid tumors in August 2021.…”

Section: Selection Of Anticancer Genes Armed In Ovsmentioning

confidence: 99%

Current landscape and perspective of oncolytic viruses and their combination therapies

Qin

2022

Translational Oncology

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Preclinical Safety Evaluation of Oncolytic Herpes Simplex Virus Type 2

Cited by 18 publications

References 18 publications

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

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

Delivery and Biosafety of Oncolytic Virotherapy

Current landscape and perspective of oncolytic viruses and their combination therapies

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