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Differential susceptibility of pediatric sarcoma cells to oncolysis by conditionally replication-competent herpes
Neeti S Bharatan1, Mark A Currier, Timothy P Cripe
1Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Purpose:
Attenuated viruses derived from herpes simplex virus (HSV) type 1 that kill tumor cells (oncolysis) are currently in clinical trials for selected cancers, primarily carcinomas and gliomas. The authors sought to determine if pediatric sarcoma cells are also sensitive to HSV-mediated oncolysis.
Materials And Methods:
The authors tested a panel of ten cell lines derived from rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and a secondary malignant fibrous histiocytoma for survival after exposure to attenuated HSV vectors. The viruses used included NV1020, haploid for the neurovirulence gene, and G207, deleted for both and ribonucleotide reductase but expressing the beta-galactosidase reporter gene. G207 transduction was determined by measuring beta-galactosidase expression.
Results:
Sarcoma cells differed in their sensitivity to viral oncolysis but were relatively consistent by histologic type. Rhabdomyosarcoma and malignant fibrous histiocytoma cells were most sensitive while osteosarcoma cells were intermediately sensitive to oncolysis by both HSV recombinants. Although Ewing sarcoma cells showed efficient viral entry and gene transfer, these cells were the least susceptible to oncolysis by HSV.
Conclusions:
Conditionally replication-competent HSV-derived vectors may be useful for the treatment of rhabdomyosarcoma and osteosarcoma, but may not be as efficacious for treating Ewing sarcoma until the mechanism of resistance is defined and circumvented.
Insights
Pediatric sarcoma cells show varied sensitivity to herpes simplex virus (HSV) oncolytic therapy. Rhabdomyosarcoma and osteosarcoma are promising candidates, while Ewing sarcoma requires further research for effective treatment.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Virology
Background:
- Attenuated herpes simplex virus (HSV) type 1 vectors are used in clinical trials for oncolysis.
- These viruses selectively kill tumor cells.
- Their efficacy in pediatric sarcomas is under investigation.
Purpose of the Study:
- To evaluate the sensitivity of pediatric sarcoma cells to HSV-mediated oncolysis.
- To determine if HSV vectors can effectively target rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and malignant fibrous histiocytoma.
Main Methods:
- Ten pediatric sarcoma cell lines were exposed to attenuated HSV vectors (NV1020 and G207).
- Cell survival was assessed post-exposure.
- Viral entry and gene transfer (using G207 and beta-galactosidase expression) were measured.
Main Results:
- Sarcoma cell sensitivity to HSV oncolysis varied by histologic type.
- Rhabdomyosarcoma and malignant fibrous histiocytoma cells were most sensitive.
- Osteosarcoma cells showed intermediate sensitivity, while Ewing sarcoma cells were least susceptible despite efficient viral entry.
Conclusions:
- Conditionally replication-competent HSV vectors show potential for treating rhabdomyosarcoma and osteosarcoma.
- Ewing sarcoma resistance to HSV oncolysis needs further investigation and strategies to overcome it.