Experimental treatment of human neuroblastoma using live-attenuated poliovirus.
Neuroblastoma, originated from neural crest cells, is the most common extracranial solid tumor in childhood. In the present study, we evaluated in vitro the oncolytic effect of live-attenuated poliovirus on human neuroblastoma cell lines, and in vivo its therapeutic efficacy in human neuroblastoma-bearing athymic mice. Live-attenuated poliovirus killed 27 (93%) of 29 established neuroblastoma cell lines in vitro. It induced cleavage of eukaryotic translation initiation factor 4G, leading to cell death through a mechanism involving activation of caspase-9, caspase-3 and poly(ADP-ribose)polymerase. For the in vivo experiments, an animal model was established using athymic mice xenotransplanted with SJ-N-JF neuroblastoma cells on both flanks. Inoculation of live-attenuated poliovirus into one of the two tumors caused a dramatic and complete regression of both the inoculated and contralateral tumors. Live-attenuated poliovirus has potent oncolytic activity against human neuroblastomas in vitro and in vivo and it may be useful for the treatment of advanced and refractory neuroblastomas, however, further studies are necessary to evaluate the safety of method.
Toyoda
Hidemi
H
Department of Pediatrics, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Ido
Masaru
M
Hayashi
Tatsuya
T
Gabazza
Esteban C
EC
Suzuki
Koji
K
Kisenge
Rodrick R
RR
Kang
Jian
J
Hori
Hiroki
H
Komada
Yoshihiro
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023321:Poliovirus Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D039603:Eukaryotic Initiation Factor-4G; D023321:Poliovirus Vaccines; D014613:Vaccines, Attenuated; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases