Effective oncolytic vaccinia therapy for human sarcomas.

Abstract

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.

• Authors: Shuangba He, Pingdong Li, Chun-Hao Chen, Richard L Bakst, Natalya Chernichenko, Yong A Yu, Nanhai Chen, Aladar A Szalay, Zhenkun Yu, Yuman Fong, Richard J Wong
• Journal: The Journal of surgical research (J Surg Res) Vol. 175 Issue 2 Pg. e53-60 (Jun 15 2012) ISSN: 1095-8673 [Electronic] United States
• PMID: 22341347 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cancer Vaccines

Topics

• Animals
• Bone Neoplasms (drug therapy, pathology)
• Cancer Vaccines (therapeutic use)
• Cell Line, Tumor
• Fibrosarcoma (drug therapy, pathology)
• Histiocytoma, Malignant Fibrous (drug therapy, pathology)
• Humans
• In Vitro Techniques
• Male
• Mice
• Mice, Nude
• Oncolytic Virotherapy
• Osteosarcoma (drug therapy, pathology)
• Rhabdomyosarcoma (drug therapy, pathology)
• Sarcoma (drug therapy, pathology)
• Soft Tissue Neoplasms (drug therapy, pathology)
• Treatment Outcome
• Vaccinia virus
• Xenograft Model Antitumor Assays