Systemic tumor-targeted sodium iodide symporter (NIS) gene therapy of hepatocellular carcinoma mediated by B6 peptide polyplexes

2017 ◽  
Vol 19 (5) ◽  
pp. e2957 ◽  
Author(s):  
Sarah Urnauer ◽  
Kathrin Klutz ◽  
Geoffrey K. Grünwald ◽  
Stephan Morys ◽  
Nathalie Schwenk ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Nis Gene

scholarly journals The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment

2021 ◽  
Author(s):  
C Spitzweg ◽  
P J Nelson ◽  
E Wagner ◽  
P Bartenstein ◽  
W Weber ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Sodium Iodide ◽  
Genetically Engineered ◽  
Oncolytic Viruses ◽  
Sodium Iodide Symporter ◽  
Preclinical Development ◽  
Therapy Strategy ◽  
Nis Gene ◽  
Disseminated Disease

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131I or alternative radionuclides, such as 188Re and 211At. Over the past 2 decades significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery, towards promising new applications in disseminated disease, in particular, through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination - critically important issues for preclinical development and clinical translation.

scholarly journals α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma

Gene Therapy ◽  
2007 ◽  
Vol 15 (3) ◽  
pp. 214-223 ◽  
Author(s):  
M J Willhauck ◽  
B R Sharif Samani ◽  
K Klutz ◽  
N Cengic ◽  
I Wolf ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter

scholarly journals The importance of sodium/iodide symporter (NIS) for thyroid cancer management

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Therapeutic Tool ◽  
Iodide Transport ◽  
Cancer Management ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene ◽  
Hormone Biosynthesis ◽  
Tumoral Cells

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

scholarly journals Application of 188Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression

2007 ◽  
Vol 92 (11) ◽  
pp. 4451-4458 ◽  
Author(s):  
Michael J. Willhauck ◽  
Bibi-Rana Sharif Samani ◽  
Franz-Josef Gildehaus ◽  
Ingo Wolf ◽  
Reingard Senekowitsch-Schmidtke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Therapeutic Effect ◽  
Half Life ◽  
Sodium Iodide ◽  
Specific Antigen ◽  
Volume Reduction ◽  
Sodium Iodide Symporter ◽  
Nis Gene

Abstract Context: We reported recently the induction of iodide accumulation in prostate cancer cells (LNCaP) by prostate-specific antigen promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131iodine (131I). These data demonstrated the potential of the NIS gene as a novel therapeutic gene, although in some extrathyroidal tumors, therapeutic efficacy may be limited by rapid iodide efflux due to a lack of iodide organification. Objective: In the current study, we therefore studied the potential of 188rhenium (188Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy β-particles than 131I. Results: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of 188Re as compared with 16% of 125I, which was sufficient for a therapeutic effect in an in vitro clonogenic assay. γ-Camera imaging of NP-1 cell xenografts in nude mice revealed accumulation of 8–16% injected dose (ID)/g 188Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for 188Re as compared with 131I. After application of 55.5 MBq 131I or 188Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after 131I treatment to 85% after application of 188Re. Conclusion: Although in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after prostate-specific antigen promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for 188Re in larger tumors.

scholarly journals Sequence defined cMET/HGFR-targeted polymers as gene delivery vehicles for the theranostic sodium iodide symporter (NIS) gene

2016 ◽  
Author(s):  
Sarah Urnauer ◽  
Stephan Morys ◽  
Ana Krhac Levacic ◽  
Andrea M Muller ◽  
Christina Schug ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Nis Gene ◽  
Delivery Vehicles ◽  
Gene Delivery Vehicles
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