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Updated: May 6, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Preclinical evaluation of engineered oncolytic herpes simplex virus for the treatment of neuroblastoma
Lauren A Gillory1, Michael L Megison, Jerry E Stewart
1Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, Alabama, United States of America.
Abstract:
Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric neural crest tumor, neuroblastoma, continues to be responsible for over 15% of pediatric cancer deaths. Novel therapeutic options are needed for this tumor. Recently, investigators have shown that mice with syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ 1 34.5 gene, enabling replication in tumor cells but precluding infection of normal neural cells. We hypothesized that M002 would also be effective in the neural crest tumor, neuroblastoma. We showed that M002 infected, replicated, and decreased survival in neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry protein for oHSV, CD111 was expressed by numerous neuroblastoma cell lines and was also present in human neuroblastoma specimens. We concluded that M002 effectively targeted neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed neuroblastoma.
Insights
Neuroblastoma, a deadly pediatric cancer, may be treatable with a novel oncolytic herpes simplex virus-1 (oHSV). This engineered virus, M002, effectively reduced neuroblastoma growth in preclinical models, offering hope for new therapies.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Neuroblastoma remains a significant cause of pediatric cancer mortality despite advances.
- Novel therapeutic strategies are urgently needed for refractory or relapsed neuroblastoma.
Purpose of the Study:
- To evaluate the efficacy of a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, against neuroblastoma.
- To determine if M002 combined with ionizing radiation enhances anti-tumor effects.
Main Methods:
- In vitro studies assessed M002 replication and cell killing in neuroblastoma cell lines.
- In vivo studies utilized murine xenograft models treated with M002, alone and with radiation.
- Expression of the oHSV entry receptor, CD111, was analyzed in neuroblastoma cell lines and patient specimens.
Main Results:
- M002 demonstrated efficient infection, replication, and decreased survival in neuroblastoma cells.
- M002 treatment significantly inhibited tumor growth in murine xenografts, with enhanced effects when combined with radiation.
- Radiation therapy improved survival without additional viral re-administration.
- CD111 was expressed on neuroblastoma cells and in human tumor samples, indicating susceptibility to oHSV.
Conclusions:
- The engineered oHSV, M002, effectively targets and reduces neuroblastoma growth.
- M002, particularly in combination with radiation, shows potential as a novel therapeutic for pediatric neuroblastoma, especially in relapsed or unresponsive cases.
