Background
Approximately one fourth of bone and soft-tissue sarcomas recur after prior treatment.
GLV-1h68 is a recombinant, replication-competent vaccinia virus that has been shown
to have oncolytic effects against many human cancer types. We sought to determine
whether GLV-1h68 could selectively target and lyse a panel of human bone and soft-tissue
sarcoma cell lines in vitro and in vivo.
Methods
GLV-1h68 was tested in a panel of four cell lines including: fibrosarcoma HT-1080,
osteosarcoma U-2OS, fibrohistiocytoma M-805, and rhabdomyosarcoma HTB-82. Gene expression,
infectivity, viral proliferation, and cytotoxicity were characterized in vitro. HT-1080 xenograft flank tumors grown in vivo were injected intratumorally with a single dose of GLV-1h68.
Results
All four cell lines supported robust viral transgene expression in vitro. At a multiplicity of infection (MOI) of five, GLV-1h68 was cytotoxic to three cell
lines, resulting in >80% cytotoxicity over 7 d. In vivo, a single injection of GLV-1h68 into HT-1080 xenografts exhibited localized intratumoral
luciferase activity peaking at d 2–4, with gradual resolution over 8 d and no evidence
of spread to normal tissues. Treated animals exhibited near-complete tumor regression
over a 28-d period without observed toxicity.
Conclusion
GLV-1h68 has potent direct oncolytic effects against human sarcoma in vitro and in vivo. Recombinant vaccinia oncolytic virotherapy could provide a new platform for the
treatment of patients with bone and soft tissue sarcomas. Future clinical trials investigating
oncolytic vaccinia as a therapy for sarcomas are warranted.
Key Words
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Article info
Publication history
Published online: December 16, 2011
Accepted:
November 23,
2011
Received:
August 12,
2011
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
