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

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Authors
Choi, Yun; Jeon, Yong-Hyun; Kang, Joo-Hyun; Chung, June-Key; Schmidt, Manuel; Kim, Chul-Woo
Issue Date
2007-02-03
Publisher
Wiley-Blackwell
Citation
Int J Cancer. 2007 May 1;120(9):1942-50.
Keywords
AnimalsCD4-Positive T-Lymphocytes/immunologyCD8-Positive T-Lymphocytes/*immunologyCancer Vaccines/*immunologyFemale*Genetic VectorsHumansInterferon-gamma/*biosynthesisMiceMice, Inbred BALB CNeoplasms, Experimental/immunology/prevention & controlSymporters/genetics/*immunologyTechnetium/diagnostic useVaccinationVaccines, DNA/*immunology
Abstract
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-gamma-secreting CD8(+) 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.
ISSN
0020-7136 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17266027

http://hdl.handle.net/10371/29787
DOI
https://doi.org/10.1002/ijc.22567
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College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
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