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Fludarabine as an Adjuvant Improves Newcastle Disease Virus-Mediated Antitumor Immunity in Hepatocellular Carcinoma.

Mol Ther Oncolytics. 2019; 
MengGang,FeiZiwei,FangMingyue,LiBinghua,ChenAnxian,XuChun,XiaMao,YuDecai,Wei
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摘要

In addition to direct oncolysis, oncolytic viruses (OVs) also induce antitumor immunity, also called viro-immunotherapy. Limited viral replication and immune-negative feedback are the major hurdles to effective viro-immunotherapy. In this study, we found that use of an adjuvant of fludarabine, a chemotherapeutic drug for chronic myeloid leukemia, increased the replication of Newcastle disease virus (NDV) by targeting signal transducer and activator of transcription 1 (STAT1), which led to enhanced oncolysis of hepatocellular carcinoma (HCC) cells. Moreover, fludarabine accelerated ubiquitin-proteasomal degradation by enhancing ubiquitylation rather than proteasomal activity. This resulted in accel... More

关键词

IDO1,Newcastle disease virus,STAT3,fludarabine,hepatocellular carcinoma,immunotherapy,myeloid-derived suppressor cells,oncolytic virus,proteasomal degrada