1. Therapeutic Efficacy of an Oncolytic Influenza Virus Carrying an Antibody Against Programmed Cell Death 1 in Hepatocellular Carcinoma
- Author
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Guanglin, Lei, Baofa, Li, Hao, Yang, Fang, Sun, Donghui, Li, Jin, Yan, Yonggang, Wang, Ruisheng, Li, Honghong, Liu, Shaogeng, Zhang, Yufeng, Li, and Penghui, Yang
- Subjects
Oncolytic Virotherapy ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Programmed Cell Death 1 Receptor ,Antibodies, Monoclonal ,Apoptosis ,Orthomyxoviridae ,Disease Models, Animal ,Mice ,Oncolytic Viruses ,Cell Line, Tumor ,Genetics ,Animals ,Humans ,Molecular Medicine ,Molecular Biology - Abstract
Oncolytic virus therapy is a promising novel immunotherapy. In this report, we engineered a novel oncolytic influenza virus (IV) carrying an antihuman programmed cell death 1 (PD-1) monoclonal antibody utilizing reverse genetics. A reassortant chimeric IV, named rFlu-huPD1, was synthesized as follows: the heavy chain of the PD-1 antibody was encoded on the PB1 fragment, and the light chain of the PD-1 antibody was encoded on the polymerase acid protein fragment. rFlu-huPD1 antibodies were produced in infected ovalantoic eggs and could replicate to high titers. Moreover, selective cytotoxicity of rFlu-huPD1 was upregulated in multiple hepatocellular carcinoma (HCC) cell lines compared with a control, as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the activation of T cells in the spleen of tumor-bearing BALB/c mice treated with rFlu-huPD1 was observed, especially cytotoxic CD8
- Published
- 2022
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