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Experimental treatment of human neuroblastoma using live-attenuated poliovirus
Hidemi Toyoda1, Masaru Ido, Tatsuya Hayashi
1Department of Pediatrics, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Abstract:
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.
Insights
Live-attenuated poliovirus demonstrates potent oncolytic activity against human neuroblastoma cells in vitro and in vivo. This poliovirus therapy shows promise for treating advanced neuroblastomas, warranting further safety evaluations.
Area of Science:
- Oncology
- Virology
- Cancer Research
Background:
- Neuroblastoma is the most common extracranial solid tumor in childhood, originating from neural crest cells.
- Current treatment options for advanced and refractory neuroblastomas are limited, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the in vitro and in vivo oncolytic effect of live-attenuated poliovirus on human neuroblastoma.
- To elucidate the mechanism of poliovirus-induced neuroblastoma cell death.
Main Methods:
- In vitro studies involved exposing 29 human neuroblastoma cell lines to live-attenuated poliovirus.
- In vivo studies utilized an athymic mouse model xenotransplanted with human neuroblastoma cells.
- Mechanistic studies assessed the cleavage of eukaryotic translation initiation factor 4G and activation of caspases.
Main Results:
- Live-attenuated poliovirus effectively killed 93% (27/29) of neuroblastoma cell lines in vitro.
- In vivo, poliovirus inoculation led to complete regression of both treated and untreated tumors in mice.
- The mechanism involved eukaryotic translation initiation factor 4G cleavage and activation of caspase-9, caspase-3, and poly(ADP-ribose)polymerase.
Conclusions:
- Live-attenuated poliovirus exhibits significant oncolytic activity against human neuroblastomas in both laboratory and animal models.
- Poliovirus therapy presents a potential new treatment avenue for advanced and refractory neuroblastomas.
- Further research is required to comprehensively assess the safety profile of this therapeutic approach.
