Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human neuroblastoma through a CD46 and nectin 4-independent pathway.
Neuroblastoma (NB) is the most common extracranial solid tumor in children. In this study, we investigated the potential antitumor capability of the engineered Edmonston strain of the carcinoembryonic antigen-expressing measles virus (MV-CEA) against human NB. The infection of a variety of NB cell lines, including SK-N-SH, SMS-KCNR, and primary NB cells, resulted in significant cytopathic effects. None of the NB cell lines showed an overexpression of the measles virus receptor CD46 and nectin 4, but the cell lines did support robust viral replication. The efficacy of this approach was examined in murine SK-N-SH xenograft models. Flow cytometry and TUNEL assays indicated an apoptotic mechanism of cell death. In summary, MV-CEA has potent therapeutic efficacy against NB mediated by a CD46- and nectin 4-independent pathway.
Department of Pediatric Surgery, Major Laboratory of the Chinese Health Ministry for Congenital Malformations, Shengjing Hospital of China Medical University, Heping District, Shenyang, PR China.
Shu-Cheng
SC
Zhang
Wei-Song
WS
Cai
Yao
Y
Zhang
Kai-Lei
KL
Jiang
Ke-Ren
KR
Zhang
Wei-Lin
WL
Wang
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000032:analysis; D045744:Cell Line, Tumor / Q000473:pathology / Q000637:transplantation / Q000821:virology; D002675:Child, Preschool; D003588:Cytopathogenic Effect, Viral; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D005822:Genetic Vectors / Q000627:therapeutic use; D015726:Giant Cells; D006801:Humans; D008297:Male; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009447:Neuroblastoma / Q000628:therapy*; D050130:Oncolytic Virotherapy; D011991:Receptors, Virus / Q000032:analysis; D014410:Tumor Stem Cell Assay; D056189:Viral Tropism; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D000075983:Nectins
D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus; C497857:CD46 protein, human; C442228:NECTIN4 protein, human; D000075983:Nectins