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

Jun, Kyong-Hwa, Gholami, Sepideh, Song, Tae-Jin, Au, Joyce, Haddad, Dana, Carson, Joshua, Chen, Chun-Hao, Mojica, Kelly, Zanzonico, Pat, Chen, Nanhai G, Zhang, Qian, Szalay, Aladar, Fong, Yuman (January 2014) A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter. Journal of Experimental and Clinical Cancer Research, 33 (1). p. 2. ISSN 0392-9078

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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 (99m)Tc 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. (99m)Tc 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 (99m)Tc 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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer > cancer types > stomach cancer therapies > viral vectors
CSHL Authors:	Gholami, Sepideh
Communities:	CSHL labs > Gholami Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 January 2014
Date Deposited:	05 Oct 2023 19:27
Last Modified:	05 Oct 2023 19:27
PMCID:	PMC3883485
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41147

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