title: Gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia virus GLV-1h153 for management of colorectal peritoneal carcinomatosis.
abstract: BACKGROUND
  Peritoneal carcinomatosis (PC) is a terminal progression of colorectal cancer (CRC). Poor response to cytoreductive operation and chemotherapy coupled with the inability to reliably track disease progression by the use of established diagnostic methods, make this a deadly disease. We examined the effectiveness of the oncolytic vaccinia virus GLV-1h153 as a therapeutic and diagnostic vehicle. We believe that viral expression of the human sodium iodide transporter (hNIS) provides both real-time monitoring of viral therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC).
  
  
  METHODS
  Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was assayed in vitro. Viral replication was examined by standard viral plaque assays. Orthotopic CRPC xenografts were generated in athymic nude mice and subsequently administered GLV-1h153 intraperitoneally. A decrease in tumor burden was assessed by mass. Orthotopic tumors were visualized by single-photon emission computed tomography/computed tomography after Iodine ((131)I) administration and by fluorescence optical imaging.
  
  
  RESULTS
  GLV-1h153 infected and killed CRC cells in a time- and concentration-dependent manner. Viral replication demonstrated greater than a 2.35 log increase in titer over 4 days. Intraperitoneal treatment of orthotopic CRPC xenografts resulted in a substantial decrease in tumor burden. Infection of orthotopic xenografts was therapeutic and facilitated monitoring by (131)I-single-photon emission computed tomography/computed tomography via expression of hNIS in infected tissue.
  
  
  CONCLUSIONS
  GLV-1h153 kills CRC in vitro effectively and decreases tumor burden in vivo. We demonstrate that GLV-1h153 can be used as an agent to provide accurate delineation of tumor burden in vivo. These findings indicate that GLV-1h153 has potential for use as a therapeutic and diagnostic agent in the treatment of CRPC.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Eveno
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Kelly
authors.initials: K
authors.lastname: Mojica
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Justin W
authors.initials: JW
authors.lastname: Ady
authors.affiliation: Division of Nuclear Medicine, Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Daniel L J
authors.initials: DL
authors.lastname: Thorek
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Valerie
authors.initials: V
authors.lastname: Longo
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Belin
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Gholami
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Clark
authors.initials: C
authors.lastname: Johnsen
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA.
authors.forename: Nanhai
authors.initials: N
authors.lastname: Chen
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA.
authors.forename: Tony
authors.initials: T
authors.lastname: Yu
authors.affiliation: Genelux Corporation, San Diego Science Center, San Diego, CA; Department of Biochemistry, University of Würzburg, Würzburg, Germany.
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: fongy@mskcc.org.
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009366:Neoplasm Seeding; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins / Q000235:genetics; D027981:Symporters / Q000235:genetics; D015899:Tomography, Emission-Computed, Single-Photon; D014616:Vaccinia virus / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D049452:Green Fluorescent Proteins; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters