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 Jun,Qian Zhang,Nanhai G Chen,Sepideh Gholami,Pat Zanzonico,Joshua Carson,Chun-Hao Chen,Dana Haddad,Tae-Jin Song,Yuman Fong,Aladar Szalay,Joyce Au,Kelly Mojica

doi:10.1186/1756-9966-33-2

Abstract

BackgroundGastric 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).MethodsGLV-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.ResultsGFP 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.ConclusionsGLV-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.

Highlights

Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments
We examined the therapeutic potential of a novel Vaccinia virus (VACV) expressing the human sodium iodide symporter, GLV-1 h153, against gastric cancers in vitro and in vivo, and tested its potential as an imaging tool
Cytotoxicity assay All five human gastric cancer cell lines were susceptible to oncolysis by GLV-1 h153 (Figure 1)

Summary

Introduction

Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Development of endoscopic or surgical resection, and more effective chemotherapies have improved the overall survival in patients with gastric cancer, the prognosis of patients with advanced gastric cancer is still poor [2,3,4]. Oncolytic viruses have great therapeutic effects against cancer cells which express high levels of ribonucleotide reductase, DNA-repair enzymes, and are resistant to apoptosis [6,7]. Many of these characteristics which make gastric cancer cells resistant to chemotherapy, make them susceptible to oncolytic viral therapy. Gene therapy using oncolytic virus offers an attractive alternative for the treatment of gastric cancer [8]

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Conclusion