title: Oncolytic Newcastle disease virus expressing chimeric antibody enhanced anti-tumor efficacy in orthotopic hepatoma-bearing mice.
abstract: BACKGROUND
  Oncolytic virus which arms the therapeutic gene to enhance anti-tumor activity is a prevalent strategy to improve oncovirotherapy of cancer. Newcastle disease virus (NDV) is a naturally oncolytic virus used for cancer therapy. Previously, we generated a mouse-human chimeric HAb18 antibody (cHAb18) against tumor-associated antigen CD147 and demonstrated the inhibition of invasion and migration of hepatocellular carcinoma (HCC) cells. Here, we constructed a recombinant NDV carrying intact cHAb18 gene (rNDV-18HL) based on Italien strain using a reverse genetics system.
  
  
  METHODS
  Recombinant rNDV-18HL was generated using reverse genetics technology. The characteristics of virally expressed cHAb18 antibody were identified by western blot, enzyme-linked immunosorbent assay, transwell invasion assay, and surface plasmon resonance technology. The biodistribution of recombinant rNDV-18HL using orthotopic xenograft mouse model was assessed with living imaging and immunohistochemistry. Kaplan-Meier survival curves and the log-rank test were performed to analyze the anti-tumor activity of rNDV-18HL.
  
  
  RESULTS
  The cHAb18 was produced in rNDV-18HL-infected cells followed by releasing into the supernatant by cytolysis. The rNDV-18HL-encoded cHAb18 antibody kept affinity for CD147 and showed inhibiting the migration and invasion of HCC cells. Viral replication and virulence were not attenuated by the incorporation of cHAb18 gene which significantly enhanced the suppression of relict tumor cell migration. The rNDV-18HL selectively replicated in orthotopic HCC xenografts leading to cHAb18 expression in situ, which induced the tumor necrosis, reduced the intrahepatic metastasis, and prolonged the survival in mice.
  
  
  CONCLUSIONS
  This study provides a new strategy of arming oncolytic NDV with therapeutic antibody to enhance anti-tumor efficacy of cancer therapy.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. wdcq@163.com.
authors.forename: Ding
authors.initials: D
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. lanliqian@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. wang_xilong@hotmail.com.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. kristy810@hotmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. lightxj@hotmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. fengfei122@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. nanren3033@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Nan
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. kingpoem01@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. v_yuncan@aliyun.com.
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. 709273401@qq.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. znchen@fmmu.edu.cn.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China. hjbian@fmmu.edu.cn.
authors.forename: Huijie
authors.initials: H
authors.lastname: Bian
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000627:therapeutic use; D051926:Basigin / Q000235:genetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy* / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D051379:Mice; D009522:Newcastle disease virus / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000627:therapeutic use*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics
chemical_list: D000906:Antibodies; C497886:BSG protein, human; D015514:Oncogene Proteins, Fusion; D051926:Basigin