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

Kyong-Hwa Jun12, Sepideh Gholami1, Tae-Jin Song13, Joyce Au1, Dana Haddad1, Joshua Carson1, Chun-Hao Chen1, Kelly Mojica1, Pat Zanzonico4, Nanhai G Chen56, Qian Zhang56, Aladar Szalay567 and Yuman Fong1*

Author Affiliations

1 Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA

2 Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

3 Department of Surgery, College of Medicine, Korea University, Seoul, Republic of Korea

4 Departments of Medical Physics and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

5 Genelux Corporation, San Diego Science Center, San Diego, CA, USA

6 Department of Radiation Oncology, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, CA, USA

7 Rudolf Virchow Center for Experimental Biomedicine, and Institute for Molecular Infection Biology, University of Wuerzburg, Wuerzburg D-97078, Germany

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Journal of Experimental & Clinical Cancer Research 2014, 33:2  doi:10.1186/1756-9966-33-2

Published: 2 January 2014

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 99mTc 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. 99mTc 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 99mTc 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.

Keywords:
Oncolytic viral therapy; GLV-1 h153; Gastric cancer; Human sodium iodide symporter (hNIS)