Effective Oncolytic Vaccinia Therapy for Human Sarcomas

• Published in: The Journal of surgical research Vol. 175; no. 2; pp. e53 - e60
• Main Authors: He, Shuangba, M.D, Li, Pingdong, M.D., Ph.D, Chen, Chun-Hao, M.D, Bakst, Richard L., M.D, Chernichenko, Natalya, M.D, Yu, Yong A., M.D, Chen, Nanhai, M.D, Szalay, Aladar A., M.D, Yu, Zhenkun, M.D., Ph.D, Fong, Yuman, M.D, Wong, Richard J., M.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2012
• Subjects: Animals; Bone Neoplasms - drug therapy; Bone Neoplasms - pathology; Cancer Vaccines - therapeutic use; Cell Line, Tumor; Fibrosarcoma - drug therapy; Fibrosarcoma - pathology; Histiocytoma, Malignant Fibrous - drug therapy; Histiocytoma, Malignant Fibrous - pathology; Humans; In Vitro Techniques; Male; Mice; Mice, Nude; oncolysis; Oncolytic Virotherapy; Osteosarcoma - drug therapy; Osteosarcoma - pathology; recombinant; replication-competent; Rhabdomyosarcoma - drug therapy; Rhabdomyosarcoma - pathology; Sarcoma - drug therapy; Sarcoma - pathology; Soft Tissue Neoplasms - drug therapy; Soft Tissue Neoplasms - pathology; Surgery; Treatment Outcome; Vaccinia virus; virus; Xenograft Model Antitumor Assays; recombinant; virus; replication-competent; oncolysis
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2011.11.1030

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.