Effective Oncolytic Vaccinia Therapy for Human Sarcomas

被引:23
作者
He, Shuangba [1 ,2 ]
Li, Pingdong [1 ,2 ]
Chen, Chun-Hao [1 ]
Bakst, Richard L. [3 ]
Chernichenko, Natalya [1 ]
Yu, Yong A. [4 ,5 ]
Chen, Nanhai [4 ,5 ]
Szalay, Aladar A. [4 ,5 ,6 ,7 ]
Yu, Zhenkun [2 ]
Fong, Yuman [1 ]
Wong, Richard J. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA
[2] Capital Med Univ, Minist Educ, Key Lab Otolaryngol Head & Neck Surg, Beijing Tongren Hosp,Dept Otolaryngol, Beijing, Peoples R China
[3] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA
[4] Genelux Corp, San Diego Sci Ctr, San Diego, CA 92109 USA
[5] Univ Calif San Diego, Dept Radiat Oncol, Moores Canc Ctr, San Diego, CA 92103 USA
[6] Univ Wurzburg, Inst Microbiol & Biochem, Bioctr, Wurzburg, Germany
[7] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Inst Microbiol & Biochem, Wurzburg, Germany
关键词
oncolysis; replication-competent; recombinant; virus; CANCER; VIRUS; POXVIRUS; VIROTHERAPY; XENOGRAFTS; GLV-1H68; TUMORS; JX-594; MICE;
D O I
10.1016/j.jss.2011.11.1030
中图分类号
R61 [外科手术学];
学科分类号
摘要
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. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:E53 / E60
页数:8
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