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, Sepideh 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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 §ssup§99m§ esup§Tc pertechnetate scintigraphy and §ssup§124§esup§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. §ssup§ 99m§esup§Tc pertechnetate scintigraphy and §ssup§124§ esup§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 §ssup§99m§esup§Tc pertechnetate scintigraphy and §ssup§124§esup§I 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.

Original languageEnglish (US)
Article number2
JournalJournal of Experimental and Clinical Cancer Research
Volume33
Issue number1
DOIs
StatePublished - Jan 2 2014
Externally publishedYes

Fingerprint

Vaccinia virus
Stomach Neoplasms
Sodium Pertechnetate Tc 99m
Radionuclide Imaging
Neoplasms
Viral Plaque Assay
Therapeutics
Oncolytic Viruses
Vaccinia
Virus Diseases
Heterografts
Nude Mice
Positron-Emission Tomography
sodium-iodide symporter
Stomach
Safety
Drug Therapy
Cell Line
Survival
Growth

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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.

In: Journal of Experimental and Clinical Cancer Research, Vol. 33, No. 1, 2, 02.01.2014.

Research output: Contribution to journalArticle

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. / A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter. In: Journal of Experimental and Clinical Cancer Research. 2014 ; Vol. 33, No. 1.
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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 §ssup§99m§ esup§Tc pertechnetate scintigraphy and §ssup§124§esup§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. §ssup§ 99m§esup§Tc pertechnetate scintigraphy and §ssup§124§ esup§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 §ssup§99m§esup§Tc pertechnetate scintigraphy and §ssup§124§esup§I 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.",
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AU - Gholami, Sepideh

AU - Song, Tae Jin

AU - Au, Joyce

AU - Haddad, Dana

AU - Carson, Joshua

AU - Chen, Chun Hao

AU - Mojica, Kelly

AU - Zanzonico, Pat

AU - Chen, Nanhai G.

AU - Zhang, Qian

AU - Szalay, Aladar

AU - Fong, Yuman

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N2 - 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 §ssup§99m§ esup§Tc pertechnetate scintigraphy and §ssup§124§esup§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. §ssup§ 99m§esup§Tc pertechnetate scintigraphy and §ssup§124§ esup§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 §ssup§99m§esup§Tc pertechnetate scintigraphy and §ssup§124§esup§I 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.

AB - 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 §ssup§99m§ esup§Tc pertechnetate scintigraphy and §ssup§124§esup§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. §ssup§ 99m§esup§Tc pertechnetate scintigraphy and §ssup§124§ esup§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 §ssup§99m§esup§Tc pertechnetate scintigraphy and §ssup§124§esup§I 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.

KW - Gastric cancer

KW - GLV-1 h153

KW - Human sodium iodide symporter (hNIS)

KW - Oncolytic viral therapy

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