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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 ( h NIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with  99m Tc pertechnetate scintigraphy and  124 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.  99m Tc pertechnetate scintigraphy and  124 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  99m Tc pertechnetate scintigraphy and  124 I microPET imaging 2 days after treatment.    Conclusions  GLV-1 h153 is an effective oncolytic virus expressing the  h NIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings.

journal of experimental and clinical cancer research

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