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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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-117716
  • 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 andBackground: 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.show moreshow less

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Metadaten
Author: Kyong-Hwa Jun, Spedideh Gholami, Tae-Jin Song, Joyce Au, Dana Haddad, Joshua Carson, Chun-Hao Chen, Kelly Mojica, Pat Zanzonico, Nanhai G. Chen, Qian Zhang, Aladar Szalay, Yuman Fong
URN:urn:nbn:de:bvb:20-opus-117716
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):Journal of Experimental & Clinical Cancer Research
ISSN:1756-9966
Year of Completion:2014
Volume:33
Issue:2
Source:Journal of Experimental & Clinical Cancer Research 2014 33:2. doi:10.1186/1756-9966-33-2
DOI:https://doi.org/10.1186/1756-9966-33-2
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24383569
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:GLV-1 h153; expression; gastric cancer; gene therapy; human sodium iodide symporter (hNIS); oncolytic viral therapy; radioiodine therapy; replication; stomach; surgery; tumors
Release Date:2015/08/24
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung