The first two authors contributed equally to this paper.
MIDGE/hNIS vaccination generates antigen-associated CD8+IFN-γ+ T cells and enhances protective antitumor immunity
Version of Record online: 31 JAN 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 120, Issue 9, pages 1942–1950, 1 May 2007
How to Cite
Choi, Y., Jeon, Y.-H., Kang, J.-H., Chung, J.-K., Schmidt, M. and Kim, a. C.-W. (2007), MIDGE/hNIS vaccination generates antigen-associated CD8+IFN-γ+ T cells and enhances protective antitumor immunity. Int. J. Cancer, 120: 1942–1950. doi: 10.1002/ijc.22567
- Issue online: 28 FEB 2007
- Version of Record online: 31 JAN 2007
- Manuscript Accepted: 4 DEC 2006
- Manuscript Received: 28 AUG 2006
- Korean Science & Engineering Foundation (KOSEF)
- antitumor vaccination;
- MIDGE vectors;
- monitoring technique;
- CD8+ T cells;
- CT26 tumor model
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-γ-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. © 2007 Wiley-Liss, Inc.