An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma Journal Article


Authors: Belin, L. J.; Ady, J. W.; Lewis, C.; Marano, D.; Gholami, S.; Mojica, K.; Eveno, C.; Longo, V.; Zanzonico, P. B.; Chen, N. G.; Szalay, A. A.; Fong, Y.
Article Title: An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma
Abstract: Background The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after 131I administration. Results GLV-1h153-infected and killed all cell lines in a time- and concentration- dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusion Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation. © 2013 Mosby, Inc. All rights reserved.
Keywords: cancer survival; controlled study; protein expression; carrier protein; unclassified drug; human cell; drug efficacy; nonhuman; mouse; animals; mice; animal tissue; tumor volume; animal experiment; animal model; in vitro study; tumor xenograft; xenograft model antitumor assays; cell line, tumor; cell assay; cancer model; survival time; iodine 131; luminescent measurements; tumor burden; drug response; oncolytic virus; oncolytic viruses; oncolytic virotherapy; pleura mesothelioma; vaccinia virus; mesothelioma; drug cytotoxicity; virus replication; single photon emission computer tomography; cancer scintiscanning; pleural neoplasms; virus culture; symporters; positron-emission tomography and computed tomography; glv 1h 153; oncolytic vaccinia virus; sodium iodine transporter
Journal Title: Surgery
Volume: 154
Issue: 3
ISSN: 0039-6060
Publisher: Elsevier Inc.  
Date Published: 2013-09-01
Start Page: 486
End Page: 495
Language: English
DOI: 10.1016/j.surg.2013.06.004
PROVIDER: scopus
PUBMED: 23890748
PMCID: PMC4123996
DOI/URL:
Notes: --- - "Export Date: 1 October 2013" - "CODEN: SURGA" - "Source: Scopus"
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MSK Authors
  1. Yuman Fong
    775 Fong
  2. Pat B Zanzonico
    355 Zanzonico
  3. Sepideh Gholami
    32 Gholami
  4. Valerie Ann Longo
    37 Longo
  5. Clarisse Adele Flora Eveno
    5 Eveno
  6. Justin William Ady
    10 Ady
  7. Laurence Justin Belin
    13 Belin
  8. Christina Lewis
    1 Lewis