title: Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter.
abstract: BACKGROUND
  Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging.
  
  
  METHODS
  Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via (99m)Tc-pertechnetate.
  
  
  RESULTS
  GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100% cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using (99m)Tc-pertechnetate.
  
  
  CONCLUSIONS
  GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Gholami
authors.forename: Dana
authors.initials: D
authors.lastname: Haddad
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy*; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters