title: Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo.
abstract: BACKGROUND
  Anaplastic thyroid carcinoma (ATC) is a fatal disease with a median survival of only 6 months. Novel therapies are needed to improve dismal outcomes.
  
  
  OBJECTIVE
  A mutated, replication-competent, vaccinia virus (GLV-1h68) has oncolytic effects on human ATC cell lines in vitro. We assessed the utility of GLV-1h68 in treating anaplastic thyroid cancer in vivo.
  
  
  METHODS
  Athymic nude mice with xenograft flank tumors of human ATCs (8505C and DRO90-1) were treated with a single intratumoral injection of GLV-1h68 at low dose (5x10(5) plaque-forming unit), high dose (5x10(6) plaque-forming unit), or PBS. Virus-mediated marker gene expression (luciferase, green fluorescent protein, and beta-galactosidase), viral biodistribution, and flank tumor volumes were measured.
  
  
  RESULTS
  Luciferase expression was detected 2 d after injection. Continuous viral replication within tumors was reflected by increasing luciferase activity to d 9. At d 10, tumor viral recovery was increased more than 50-fold as compared with the injected dose, and minimal virus was recovered from the lung, liver, brain, heart, spleen, and kidneys. High-dose virus directly injected into normal tissues was undetectable at d 10. The mean volume of control 8505C tumors increased 50.8-fold by d 45, in contrast to 10.5-fold (low dose) and 2.1-fold (high dose; P=0.028) increases for treated tumors. DRO90-1 tumors also showed significant growth inhibition by high-dose virus. No virus-related toxicity was observed throughout the study.
  
  
  CONCLUSIONS
  GLV-1h68 efficiently infects, expresses transgenes within, and inhibits the growth of ATC in vivo. These promising findings support future clinical trials for patients with ATC.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Shu-Fu
authors.initials: SF
authors.lastname: Lin
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Price
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Brader
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.forename: Lorena
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
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: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000473:pathology; D014183:Transplantation, Heterologous; D014616:Vaccinia virus / Q000276:immunology*; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D005819:Genetic Markers; D014765:Viral Vaccines