Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus
<p>Abstract</p> <p>Introduction</p> <p>Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide sym...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-03-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/9/1/36 |
| _version_ | 1819057866465607680 |
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| author | Mittra Arjun Au Joyce Carson Joshua Carpenter Susanne G Gonzalez Lorena Yu Yong A Chen Chun-Hao Zhang Qian Chen Nanhai G Haddad Dana Gonen Mithat Zanzonico Pat B Fong Yuman Szalay Aladar A |
| author_facet | Mittra Arjun Au Joyce Carson Joshua Carpenter Susanne G Gonzalez Lorena Yu Yong A Chen Chun-Hao Zhang Qian Chen Nanhai G Haddad Dana Gonen Mithat Zanzonico Pat B Fong Yuman Szalay Aladar A |
| author_sort | Mittra Arjun |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Introduction</p> <p>Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (<it>hNIS</it>) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153.</p> <p>Methods</p> <p>GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry <it>hNIS </it>via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of <it>hNIS </it>in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free <sup>124</sup>I radiotracer.</p> <p>Results</p> <p>GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of <it>hNIS </it>expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). <it>In vivo</it>, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via <sup>124</sup>I-PET.</p> <p>Conclusion</p> <p>Insertion of the <it>hNIS </it>gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.</p> |
| first_indexed | 2024-12-21T13:46:07Z |
| format | Article |
| id | doaj.art-140ca320fa274781b8daa4bad10204cf |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T13:46:07Z |
| publishDate | 2011-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-140ca320fa274781b8daa4bad10204cf2022-12-21T19:01:51ZengBMCJournal of Translational Medicine1479-58762011-03-01913610.1186/1479-5876-9-36Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virusMittra ArjunAu JoyceCarson JoshuaCarpenter Susanne GGonzalez LorenaYu Yong AChen Chun-HaoZhang QianChen Nanhai GHaddad DanaGonen MithatZanzonico Pat BFong YumanSzalay Aladar A<p>Abstract</p> <p>Introduction</p> <p>Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (<it>hNIS</it>) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153.</p> <p>Methods</p> <p>GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry <it>hNIS </it>via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of <it>hNIS </it>in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free <sup>124</sup>I radiotracer.</p> <p>Results</p> <p>GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of <it>hNIS </it>expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). <it>In vivo</it>, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via <sup>124</sup>I-PET.</p> <p>Conclusion</p> <p>Insertion of the <it>hNIS </it>gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.</p>http://www.translational-medicine.com/content/9/1/36 |
| spellingShingle | Mittra Arjun Au Joyce Carson Joshua Carpenter Susanne G Gonzalez Lorena Yu Yong A Chen Chun-Hao Zhang Qian Chen Nanhai G Haddad Dana Gonen Mithat Zanzonico Pat B Fong Yuman Szalay Aladar A Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus Journal of Translational Medicine |
| title | Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus |
| title_full | Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus |
| title_fullStr | Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus |
| title_full_unstemmed | Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus |
| title_short | Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus |
| title_sort | insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus |
| url | http://www.translational-medicine.com/content/9/1/36 |
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