Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent prog...Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent progress in genetic engineering,coupled with experiential insights,offers opportunities to enhance the therapeutic efficacy of the influenza A virus.This review explores the use of the influenza virus,its attenuated forms,and associated vaccines in cancer immunotherapy,highlighting their respective advantages and challenges.We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors,aiming to maximize their clinical impact.Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.展开更多
Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candi...Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candidate vaccine viruses(CVVs).Methods In accordance with the World Health Organization(WHO) recommendations, we constructed two reassortant viruses using reverse genetics(RG) technology to match the two different epidemic H5 N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo.Results The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs.Conclusion We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics,which may aid in our preparedness for a potential H5N6 pandemic.展开更多
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2022R01002)the National Natural Science Foundation of China(Nos.82272300 and 82102893)the Fundamental Research Funds for the Central Universities(No.226-2024-00062),China.
文摘Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent progress in genetic engineering,coupled with experiential insights,offers opportunities to enhance the therapeutic efficacy of the influenza A virus.This review explores the use of the influenza virus,its attenuated forms,and associated vaccines in cancer immunotherapy,highlighting their respective advantages and challenges.We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors,aiming to maximize their clinical impact.Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
基金This study was supported by the National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China[No.2018ZX10711001,2018ZX10305409-004-002]Emergency Prevention and Control Project of Ministry of Science and Technology of China[No.10600100000015001206].
文摘Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candidate vaccine viruses(CVVs).Methods In accordance with the World Health Organization(WHO) recommendations, we constructed two reassortant viruses using reverse genetics(RG) technology to match the two different epidemic H5 N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo.Results The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs.Conclusion We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics,which may aid in our preparedness for a potential H5N6 pandemic.