title: Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human hepatoblastoma.
abstract: BACKGROUND
  Hepatoblastoma (HB) is the most common primary, malignant pediatric liver tumor in children. The treatment results for affected children have markedly improved in recent decades. However, the prognosis for high-risk patients who have extrahepatic extensions, invasion of the large hepatic veins, distant metastases and very high alpha-fetoprotein (AFP) serum levels remains poor. There is an urgent need for the development of novel therapeutic approaches.
  
  
  METHODS
  An attenuated strain of measles virus, derived from the Edmonston vaccine lineage, was genetically engineered to produce carcinoembryonic antigen (CEA). We investigated the antitumor potential of this novel viral agent against human HB both in vitro and in vivo.
  
  
  RESULTS
  Infection of the Hep2G and HUH6 HB cell lines, at multiplicities of infection (MOIs) ranging from 0.01 to 1, resulted in a significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72-96 h after infection. Both of the HB lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. The efficacy of this approach in vivo was examined in murine Hep2G xenograft models. Flow cytometry assays indicated an apoptotic mechanism of cell death. Intratumoral administration of MV-CEA resulted in statistically significant delay of tumor growth and prolongation of survival.
  
  
  CONCLUSIONS
  The engineered measles virus Edmonston strain MV-CEA has potent therapeutic efficacy against HB cell lines and xenografts. Trackable measles virus derivatives merit further exploration in HB treatment.
authors.affiliation: Department of Pediatric Surgery, Major Laboratory of Chinese Health Ministry for Congenital Malformations, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang 110004, P.R. China. zhangshucheng76@126.com
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Zhang
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Wang
authors.forename: Wei-Song
authors.initials: WS
authors.lastname: Cai
authors.forename: Kai-Lei
authors.initials: KL
authors.lastname: Jiang
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D008459:Measles virus / Q000235:genetics*; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D002272:Carcinoembryonic Antigen; D051916:Membrane Cofactor Protein