A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter Journal Article


Authors: Jun, K. H.; Gholami, S.; Song, T. J.; Au, J.; Haddad, D.; Carson, J.; Chen, C. H.; Mojica, K.; Zanzonico, P.; Chen, N. G.; Zhang, Q.; Szalay, A.; Fong, Y.
Article 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 §ssup§99m§ esup§Tc pertechnetate scintigraphy and §ssup§124§esup§I 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. §ssup§ 99m§esup§Tc pertechnetate scintigraphy and §ssup§124§ esup§I 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 §ssup§99m§esup§Tc pertechnetate scintigraphy and §ssup§124§esup§I 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. © 2014 Jun et al.; licensee BioMed Central Ltd.
Keywords: gastric cancer; oncolytic viral therapy; glv-1 h153; human sodium iodide symporter (hnis)
Journal Title: Journal of Experimental & Clinical Cancer Research
Volume: 33
Issue: 1
ISSN: 1756-9966
Publisher: Biomed Central Ltd  
Date Published: 2014-01-02
Start Page: 2
Language: English
DOI: 10.1186/1756-9966-33-2
PROVIDER: scopus
PMCID: PMC3883485
PUBMED: 24383569
DOI/URL:
Notes: Export Date: 3 February 2014 -- CODEN: JECRD -- Source: Scopus
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MSK Authors
  1. Yuman Fong
    745 Fong
  2. Chun-Hao Chen
    35 Chen
  3. Dana Haddad
    18 Haddad
  4. Pat B Zanzonico
    246 Zanzonico
  5. Sepideh Gholami
    27 Gholami
  6. Kyonghwa Jun
    3 Jun
  7. Taejin Song
    7 Song
  8. Joyce Au
    12 Au
  9. Joshua S Carson
    12 Carson