Effective oncolytic vaccinia therapy for human sarcomas Journal Article

Authors: He, S.; Li, P.; Chen, C. H.; Bakst, R. L.; Chernichenko, N.; Yu, Y. A.; Chen, N.; Szalay, A. A.; Yu, Z.; Fong, Y.; Wong, R. J.
Article Title: 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. © 2012 Elsevier Inc. All rights reserved.
Keywords: osteosarcoma; unclassified drug; human cell; gene expression; green fluorescent protein; in vivo study; cancer cell culture; cytotoxicity; in vitro study; tumor regression; tumor xenograft; sarcoma; fibrosarcoma; human cell culture; transgene; oncolytic virus; oncolytic virotherapy; vaccinia virus; soft tissue sarcoma; virus infection; virus recombinant; virus replication; rhabdomyosarcoma; virus; recombinant; oncolysis; replication-competent; fibrohistiocytoma; glv 1h 68
Journal Title: Journal of Surgical Research
Volume: 175
Issue: 2
ISSN: 0022-4804
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2012-06-15
Start Page: e53
End Page: e60
Language: English
DOI: 10.1016/j.jss.2011.11.1030
PROVIDER: scopus
PMCID: PMC3350611
PUBMED: 22341347
Notes: --- - "Export Date: 4 June 2012" - "CODEN: JSGRA" - "Source: Scopus"
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MSK Authors
  1. Richard J Wong
    230 Wong
  2. Richard L Bakst
    15 Bakst
  3. Yuman Fong
    745 Fong
  4. Chun-Hao Chen
    35 Chen
  5. Shuangba He
    11 He
  6. Pingdong Li
    5 Li