An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma

Laurence J. Belin, Justin W. Ady, Christina Lewis, Drew Marano, Sepideh Gholami, Kelly Mojica, Clarisse Eveno, Valerie Longo, Pat B. Zanzonico, Nanhai G. Chen, Aladar A. Szalay, Yuman Fong

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after 131I administration. Results GLV-1h153-infected and killed all cell lines in a time- and concentration- dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusion Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation.

Original languageEnglish (US)
Pages (from-to)486-495
Number of pages10
JournalSurgery (United States)
Volume154
Issue number3
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

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Oncolytic Viruses
Symporters
Vaccinia virus
Iodine
Sodium
Heterografts
Survival
Tumor Burden
Nude Mice
Viral Plaque Assay
Cell Line
Mesothelioma
Therapeutics
Malignant Mesothelioma
Single Photon Emission Computed Tomography Computed Tomography
Infection
Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma. / Belin, Laurence J.; Ady, Justin W.; Lewis, Christina; Marano, Drew; Gholami, Sepideh; Mojica, Kelly; Eveno, Clarisse; Longo, Valerie; Zanzonico, Pat B.; Chen, Nanhai G.; Szalay, Aladar A.; Fong, Yuman.

In: Surgery (United States), Vol. 154, No. 3, 01.09.2013, p. 486-495.

Research output: Contribution to journalArticle

Belin, Laurence J. ; Ady, Justin W. ; Lewis, Christina ; Marano, Drew ; Gholami, Sepideh ; Mojica, Kelly ; Eveno, Clarisse ; Longo, Valerie ; Zanzonico, Pat B. ; Chen, Nanhai G. ; Szalay, Aladar A. ; Fong, Yuman. / An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma. In: Surgery (United States). 2013 ; Vol. 154, No. 3. pp. 486-495.
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abstract = "Background The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after 131I administration. Results GLV-1h153-infected and killed all cell lines in a time- and concentration- dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusion Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation.",
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T1 - An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma

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AU - Ady, Justin W.

AU - Lewis, Christina

AU - Marano, Drew

AU - Gholami, Sepideh

AU - Mojica, Kelly

AU - Eveno, Clarisse

AU - Longo, Valerie

AU - Zanzonico, Pat B.

AU - Chen, Nanhai G.

AU - Szalay, Aladar A.

AU - Fong, Yuman

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N2 - Background The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after 131I administration. Results GLV-1h153-infected and killed all cell lines in a time- and concentration- dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusion Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation.

AB - Background The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after 131I administration. Results GLV-1h153-infected and killed all cell lines in a time- and concentration- dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusion Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation.

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