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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Shuangba
authors.initials: S
authors.lastname: He
authors.forename: Pingdong
authors.initials: P
authors.lastname: Li
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bakst
authors.forename: Natalya
authors.initials: N
authors.lastname: Chernichenko
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.forename: Nanhai
authors.initials: N
authors.lastname: Chen
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Yu
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology; D051677:Histiocytoma, Malignant Fibrous / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014616:Vaccinia virus; D023041:Xenograft Model Antitumor Assays
chemical_list: D019496:Cancer Vaccines