title: A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter.
abstract: BACKGROUND
  Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. We investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hNIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with (99m)Tc pertechnetate scintigraphy and ¹²⁴I positron emission tomography (PET).
  
  
  METHODS
  GLV-1 h153 was tested against five human gastric cancer cell lines using cytotoxicity and standard viral plaque assays. In vivo, subcutaneous flank tumors were generated in nude mice with human gastric cancer cells, MKN-74. Tumors were subsequently injected with either GLV-1 h153 or PBS and followed for tumor growth. (99m)Tc pertechnetate scintigraphy and ¹²⁴I microPET imaging were performed.
  
  
  RESULTS
  GFP expression, a surrogate for viral infectivity, confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1, GLV-1 h153 achieved > 90% cytotoxicity in MNK-74, OCUM-2MD3, and AGS over 9 days, and >70% cytotoxicity in MNK- 45 and TMK-1. In vivo, GLV-1 h153 was effective in treating xenografts (p < 0.001) after 2 weeks of treatment. GLV-1 h153-infected tumors were readily imaged by (99m)Tc pertechnetate scintigraphy and ¹²⁴I microPET imaging 2 days after treatment.
  
  
  CONCLUSIONS
  GLV-1 h153 is an effective oncolytic virus expressing the hNIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings.
authors.forename: Kyong-Hwa
authors.initials: KH
authors.lastname: Jun
authors.forename: Sepideh
authors.initials: S
authors.lastname: Gholami
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Song
authors.forename: Joyce
authors.initials: J
authors.lastname: Au
authors.forename: Dana
authors.initials: D
authors.lastname: Haddad
authors.forename: Joshua
authors.initials: J
authors.lastname: Carson
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Kelly
authors.initials: K
authors.lastname: Mojica
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Aladar
authors.initials: A
authors.lastname: Szalay
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA. fongy@mskcc.org.
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D027981:Symporters / Q000235:genetics*; D047368:Tumor Burden; D014616:Vaccinia virus / Q000235:genetics*; D014779:Virus Replication; D000099209:Sodium-Iodide Symporters
chemical_list: D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters