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Article

MICA/IL-12: A novel bifunctional protein for killer cell activation

  • Authors:
    • Ashlee Tietje
    • Xi Yang
    • Xianzhong Yu
    • Yanzhang Wei
  • View Affiliations / Copyright

    Affiliations: Division of Science, Southern Wesleyan University, Central, SC 29634, USA, Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA
  • Pages: 1889-1895
    |
    Published online on: January 16, 2017
       https://doi.org/10.3892/or.2017.5375
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Abstract

Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors such as NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce the expression of these ligands, leaving them less detectable by NK cells. Along with these receptors, NK cells also require activating cytokines, such as IL-12. A previous study in our laboratory showed that a fusion protein of the extracellular domain of mouse UL-16 binding protein-like transcript 1 (MULT1E) and mouse interleukin 12 (IL-12) can effectively activate mouse NK cells by in vitro assays and in vivo in animal tumor models. The aim of the present study was to expand the concept of developing a novel bifunctional fusion protein for enhanced NK cell activation to human killer cells. The proposed protein combines the extracellular domain of a human NKG2D ligand, MHC class I polypeptide-related sequence A (MICA) and IL-12. It is hypothesized that when expressed by tumor cells, the protein will activate human NK and other killer cells using the NKG2D receptor, and deliver IL-12 to the NK cells where it can interact with the IL-12R and enhance cytotoxicity. The fusion protein, when expressed by engineered tumor cells, indeed activated NK92 cells as measured by an increase in interferon-γ (IFN-γ) production and an increase in cytotoxicity of tumor cells. The fusion protein was also able to increase the proliferation of human peripheral blood mononuclear cells (PBMCs) and augment their production of IFN-γ. This study along with the data from the previous mouse studies suggest that the MICA/IL-12 bifunctional fusion protein represents an effective activator of killer cells for cancer treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Tietje A, Yang X, Yu X and Wei Y: MICA/IL-12: A novel bifunctional protein for killer cell activation. Oncol Rep 37: 1889-1895, 2017.
APA
Tietje, A., Yang, X., Yu, X., & Wei, Y. (2017). MICA/IL-12: A novel bifunctional protein for killer cell activation. Oncology Reports, 37, 1889-1895. https://doi.org/10.3892/or.2017.5375
MLA
Tietje, A., Yang, X., Yu, X., Wei, Y."MICA/IL-12: A novel bifunctional protein for killer cell activation". Oncology Reports 37.3 (2017): 1889-1895.
Chicago
Tietje, A., Yang, X., Yu, X., Wei, Y."MICA/IL-12: A novel bifunctional protein for killer cell activation". Oncology Reports 37, no. 3 (2017): 1889-1895. https://doi.org/10.3892/or.2017.5375
Copy and paste a formatted citation
x
Spandidos Publications style
Tietje A, Yang X, Yu X and Wei Y: MICA/IL-12: A novel bifunctional protein for killer cell activation. Oncol Rep 37: 1889-1895, 2017.
APA
Tietje, A., Yang, X., Yu, X., & Wei, Y. (2017). MICA/IL-12: A novel bifunctional protein for killer cell activation. Oncology Reports, 37, 1889-1895. https://doi.org/10.3892/or.2017.5375
MLA
Tietje, A., Yang, X., Yu, X., Wei, Y."MICA/IL-12: A novel bifunctional protein for killer cell activation". Oncology Reports 37.3 (2017): 1889-1895.
Chicago
Tietje, A., Yang, X., Yu, X., Wei, Y."MICA/IL-12: A novel bifunctional protein for killer cell activation". Oncology Reports 37, no. 3 (2017): 1889-1895. https://doi.org/10.3892/or.2017.5375
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