TY  - JOUR
A1  - Jun, Kyong-Hwa
A1  - Gholami, Spedideh
A1  - Song, Tae-Jin
A1  - Au, Joyce
A1  - Haddad, Dana
A1  - Carson, Joshua
A1  - Chen, Chun-Hao
A1  - Mojica, Kelly
A1  - Zanzonico, Pat
A1  - Chen, Nanhai G.
A1  - Zhang, Qian
A1  - Szalay, Aladar
A1  - Fong, Yuman
T1  - A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter
JF  - Journal of Experimental & Clinical Cancer Research
N2  - 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 Tc-99m pertechnetate scintigraphy and I-124 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. Tc-99m pertechnetate scintigraphy and I-124 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 Tc-99m pertechnetate scintigraphy and I-124 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.
KW  - oncolytic viral therapy
KW  - GLV-1 h153
KW  - gastric cancer
KW  - human sodium iodide symporter (hNIS)
KW  - radioiodine therapy
KW  - gene therapy
KW  - expression
KW  - replication
KW  - stomach
KW  - tumors
KW  - surgery
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117716
SN  - 1756-9966
VL  - 33
IS  - 2
ER  -