Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter

Sepideh Gholami, Dana Haddad, Chun Hao Chen, Nanhai G. Chen, Qian Zhang, Pat B. Zanzonico, Aladar A. Szalay, Yuman Fong

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging. Methods: Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via 99mTc-pertechnetate. Results: GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100% cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using 99mTc-pertechnetate. Conclusion: GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.

Original languageEnglish (US)
Pages (from-to)1040-1047
Number of pages8
JournalSurgery
Volume150
Issue number6
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

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Oncolytic Viruses
Symporters
Vaccinia virus
Iodine
Sodium
Sodium Pertechnetate Tc 99m
Therapeutics
Viral Plaque Assay
Infection
sodium-iodide symporter
Anaplastic Thyroid Carcinoma
Cell Line
Virus Diseases
Heterografts
Radiotherapy

ASJC Scopus subject areas

  • Surgery

Cite this

Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter. / Gholami, Sepideh; Haddad, Dana; Chen, Chun Hao; Chen, Nanhai G.; Zhang, Qian; Zanzonico, Pat B.; Szalay, Aladar A.; Fong, Yuman.

In: Surgery, Vol. 150, No. 6, 01.12.2011, p. 1040-1047.

Research output: Contribution to journalArticle

Gholami, Sepideh ; Haddad, Dana ; Chen, Chun Hao ; Chen, Nanhai G. ; Zhang, Qian ; Zanzonico, Pat B. ; Szalay, Aladar A. ; Fong, Yuman. / Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter. In: Surgery. 2011 ; Vol. 150, No. 6. pp. 1040-1047.
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abstract = "Background: Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging. Methods: Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via 99mTc-pertechnetate. Results: GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100{\%} cytotoxicity in 8305c and FRO by day 5 and 70{\%} in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using 99mTc-pertechnetate. Conclusion: GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.",
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T1 - Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter

AU - Gholami, Sepideh

AU - Haddad, Dana

AU - Chen, Chun Hao

AU - Chen, Nanhai G.

AU - Zhang, Qian

AU - Zanzonico, Pat B.

AU - Szalay, Aladar A.

AU - Fong, Yuman

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N2 - Background: Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging. Methods: Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via 99mTc-pertechnetate. Results: GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100% cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using 99mTc-pertechnetate. Conclusion: GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.

AB - Background: Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging. Methods: Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via 99mTc-pertechnetate. Results: GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100% cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using 99mTc-pertechnetate. Conclusion: GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.

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