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

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-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.

Inhibition of Lewis Lung Carcinoma Growth by Toxoplasma gondii through Induction of Th1 Immune Responses and Inhibition of Angiogenesis

“…These results indicate that Th1 immune responses were depressed in Lewis lung carcinoma, and show that the production of cytokines such as IFN-γ, TNF-α, IL-12, and IL-2 can arrest proliferation of malignant cells and prevent the angiogenesis necessary for tumor growth (3, 5, 17, 21, 22). Similar results were reported in melanoma, liver cancer, and thyroid cancer (22-24). And these phenomena were also confirmed in the titrations of the IgG subclasses.…”

Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma

“…Studies have shown the presence of auto antibodies against NIS in a subset of autoimmunity induced thyroiditis patients [39] indicating NIS could act as antigen. In mouse tumor models expressing human NIS (hNIS), repeated DNA vaccination with hNIS induced NIS associated CD4 and CD8 T-cell immune response along with improved efficacy [40]. It is likely that at least in mouse tumor models hNIS (86.2% sequence similarity with mouse NIS) [41] could act as foreign antigen and induce hNIS-specific T cells.…”

Human sodium iodide symporter gene adjunctive radiotherapy to enhance the preventive effect of hMUC1 DNA vaccine

“…The other mechanism, which might be involved, is that the released hNIS itself from dead cells after radionuclide treatment could also raise immune response against viable CNMF cells with hNIS expression. We recently reported that hNIS vaccination with MIDGE plasmid vector could raise hNIS‐associated cell mediated immune responses in mice tumor model 46…”