Differential susceptibility of pediatric sarcoma cells to oncolysis by conditionally replication-competent herpes simplex viruses.
OBJECTIVE
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.


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.
Bharatan
Neeti S
NS
Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Currier
Mark A
MA
Cripe
Timothy P
TP
D002470:Cell Survival; D002648:Child; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology / Q000821:virology; D012208:Rhabdomyosarcoma / Q000473:pathology / Q000821:virology; D012512:Sarcoma, Ewing / Q000473:pathology / Q000821:virology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000473:pathology* / Q000821:virology*; D014779:Virus Replication / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase