Oncolytic Activity of Wild-type Newcastle Disease Virus HK84 Against Hepatocellular Carcinoma Associated with Activation of Type I Interferon Signaling  

作　　者：Liming Chen Yongdong Niu Jiating Sun Hong Lin Guoxi Liang Min Xiao Dongmei Shi Jia Wang Huachen Zhu Yi Guan 

机构地区：[1]Department of Oncology,First Affiliated Hospital of Shantou University Medical College,Shantou,Guangdong,China [2]In-ternational Joint Laboratory for Virology and Emerging Infectious Diseases(Ministry of Education),Guangdong-Hong Kong Joint Laboratory for Emerging Infectious Diseases,Joint Institute of Virology of STU/HKU,Shantou,Guangdong,China [3]Department of Pharmacology,Shantou University Medical College,Shantou,Guangdong,China

出　　处：《Journal of Clinical and Translational Hepatology》2022年第2期284-296,共13页临床与转化肝病杂志（英文版）

基　　金：supported by research grants from the Guangdong Science and Technology Innovation Strategy Special Found(2019B121205009);the Guangdong Science and Technology Special Found(190830095586328 and 200109155890863)and the Li Ka Shing Foundation.

摘　　要：Background and Aims:Hepatocellular carcinoma(HCC)is listed as one of the most common causes of cancer-related death.Oncolytic therapy has become a promising treatment because of novel immunotherapies and gene editing technology,but biosafety concerns remain the biggest limitation for clinical application.We studied the the antitumor activity and biosafety of the wild-type Newcastle disease virus HK84 strain(NDV/HK84)and 10 other NDV strains.Meth-ods:Cell proliferation and apoptosis were determined by cell counting Kit-8 and fluorescein isothiocyanate Annexin V apoptosis assays.Colony formation,wound healing,and a xenograft mouse model were used to evaluate in vivo and in vitro oncolytic effectiveness.The safety of NDV/HK84 was tested in nude mice by an in vivo luciferase imaging system.The replication kinetics of NDV/HK84 in normal tis-sues and tumors were evaluated by infectious-dose assays in eggs.RNA sequencing analysis was performed to explore NDV/HK84 activity and was validated by quantitative real-time PCR.Results:The cell counting Kit-8 assays of vi-ability found that the oncolytic activity of the NDV strains differed with the multiplicity of infection(MOI).At an MOI of 20,the oncolytic activity of all NDV strains except the DK/JX/21358/08 strain was>80%.The oncolytic activities of the NDV/HK84 and DK/JX/8224/04 strains were>80%at both MOI=20 and MOI=2.Only NDV/HK84 had>80%oncolytic activities at both MOI=20 and MOI=2.We chose NDV/HK84 as the candidate virus to test the oncolytic effect of NDV in HCC in the in vitro and in vivo experiments.NDV/HK84 killed human SK-HEP-1 HCC cells without affecting healthy cells.Conclusions:Intratumor infection with NDV/HK84 strains compared with vehicle controls or positive controls indicated that NDV/HK84 strain specifically inhib-ited HCC without affecting healthy mice.High-throughput RNA sequencing showed that the oncolytic activity of NDV/HK84 was dependent on the activation of type I interferon signaling.

关 键 词：Newcastle disease virus Oncolytic effectiveness Type I interferon Hepatocellular carcinoma BIOSAFETY 

分 类 号：S85[农业科学—兽医学]