Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

Dwyer, Róisín M.; Bergert, Elizabeth R.; O’Connor, Michael K.; Gendler, Sandra J.; Morris, John C.

doi:10.1038/sj.gt.3302599

Cited by 57 publications

(36 citation statements)

References 27 publications

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“…39,40 Using sodium iodide symporter, targeted radionuclide gene therapy has been performed to promote treatment of various types of cancer. Some investigators found that effective gene expression is induced in living subjects by infection of NIS expressing nonviral or viral vector into cancer cell and it provides a good therapeutic index in preclinical model.…”

Section: Discussionmentioning

confidence: 99%

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Choi¹,

Jeon²,

Kang³

et al. 2007

Intl Journal of Cancer

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Human sodium iodide symporter (hNIS) is a transmembrane protein that actively transports iodide ions into thyroid cells. hNIS is over-expressed in some cases of the thyroid cancers compared with the surrounding normal tissues and has been considered to be an attractive target for immunotherapy. The aim of this study is to determine the feasibility of utilizing the hNIS antigenic protein in enhanced-antigen-associated immunotherapy using image analysis with a gamma counter. To accomplish this, minimalistic immunogenically defined gene expression (MIDGE), either plain or coupled to a nuclear localization signal (NLS) peptide, was used as a vector system. Vaccination with MIDGE/hNIS, MIDGE/ hNIS-NLS and pcDNA3.1/hNIS produced a significant increase in the number of hNIS-associated IFN-c-secreting CD8 1 T cells, with MIDGE/hNIS having the strongest effect. In addition, immunization with the hNIS encoding vectors induced antigen-mediated antitumor activity against NIS-expressing CT26 tumors in vivo, with the highest tumor free rate (100%) and lowest tumor growth being observed up to 40 days after the CT26/NIS tumor challenge with MIDGE/hNIS than those resulting from other immunization groups. Tumor progression could be followed noninvasively and repetitively by monitoring levels of hNIS gene expression in the tumors using scintigraphic image analysis. Overall, hNIS has a potential use as an antigen for immunization approaches, and vaccination with MIDGE/hNIS vectors is an effective means of generating hNIS-associated immune responses in mice. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Choi¹,

Jeon²,

Kang³

et al. 2007

Intl Journal of Cancer

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“…Several investigators have described tissue-specific delivery methods of therapeutic genes in various cancer models using an adenoviral system. [19][20][21][22] These investigators have shown that an adenovirus-mediated gene delivery system can induce strong expression of therapeutic genes and effective anti-tumor effects in some cancer models.…”

Section: Discussionmentioning

confidence: 99%

Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

et al. 2010

Cancer Gene Ther

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Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR1) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared with control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR1-and Ad-hNIS-infected cells, but not for control cells. In vivo uptake of Tc99m sestamibi and Tc-99m pertechnetate was twofold and 10-fold higher for Ad-shMDR1 and Ad-hNIS-infected tumors as compared with tumors infected with a control adenovirus construct that expressed b-galactrosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have shown successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes.

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“…Furthermore, this correlated with a reduced level of NIS protein expression on western blot analysis [134]. Most subsequent studies have employed low-iodine diets combined with T4 supplementation (0.05-5 mg/l) for 1-2 weeks prior to radioiodide therapy [128,[150][151][152][153]. The effectiveness and feasibility of using this protocol can be gauged from the study by Wapnir et al (2004) that was performed in patients with metastatic breast cancer [109].…”

Section: Thyroid Gland Suppression As a Strategy During Nis Gene Therapymentioning

confidence: 99%

“…Most commonly, NIS gene expression has been mapped using pertechnetate ( 99m TcO 4 − )-or iodide ( 123 I)-based scintigraphic techniques with conventional gamma camera imaging [138,[150][151][152] or SPECT/CT [153]. Scintigraphic assessment enables estimation of the level of radioisotope uptake and the effective half-life within the NIS-transduced tumour, which may then be employed to provide reliable estimates of the tumour absorbed dose.…”

Section: Nis As Reporter Genementioning

confidence: 99%

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

Hingorani¹

2010

CCDT

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The sodium iodide symporter (NIS) is responsible for thyroidal, salivary, gastric, intestinal and mammary iodide uptake. It was first cloned from the rat in 1996 and shortly thereafter from human and mouse tissue. In the intervening years, we have learned a great deal about the biology of NIS. Detailed knowledge of its genomic structure, transcriptional and post-transcriptional regulation and pharmacological modulation has underpinned the selection of NIS as an exciting approach for targeted gene delivery. A number of in vitro and in vivo studies have demonstrated the potential of using NIS gene therapy as a means of delivering highly conformal radiation doses selectively to tumours. This strategy is particularly attractive because it can be used with both diagnostic ( 99m Tc, 125 I, 124 I) and therapeutic ( 131 I, 186 Re, 188 Re, 211 At) radioisotopes and it lends itself to incorporation with standard treatment modalities, such as radiotherapy or chemoradiotherapy. In this article, we review the biology of NIS and discuss its development for gene therapy.

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Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

Cited by 57 publications

References 27 publications

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

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Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

Cited by 57 publications

References 27 publications

MIDGE/hNIS vaccination generates antigen‐associated CD8+IFN‐γ+ T cells and enhances protective antitumor immunity

MIDGE/hNIS vaccination generates antigen‐associated CD8+IFN‐γ+ T cells and enhances protective antitumor immunity

Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

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MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity