An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation

  • Authors:
    • Lining Zhu
    • Zhihui Zhao
    • Yanzhang Wei
    • William Marcotte
    • Thomas E. Wagner
    • Xianzhong Yu
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  • Published online on: May 8, 2012     https://doi.org/10.3892/ijo.2012.1466
  • Pages: 661-669
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Abstract

The dependency of activated natural killer (NK) cells on the continuous support of exogenous interleukin (IL)-2 for their in vivo survival, tumor localization and consequently, their antitumor effect, is a major obstacle for NK cell-mediated tumor therapy. In the present study, a fusion gene between IL-12 and mouse sonic hedgehog C-terminal domain (Shh-C) was constructed. The fusion protein was autocatalytically processed to form cholesterol-modified IL-12 molecules and an autocrine loop of IL-12 was established for the sustained activation of NK cells. The transduced NK cells matured more rapidly in vitro with the enhanced expression of granule-related proteins. NKIL-12/Shh-C cells reached the same proliferation rate as NK cells transduced with enhanced green fluorescent protein (EGFP)/Shh-C (NKEGFP/Shh-C) with <10-fold IL-2 supplementation, suggesting that the fusion protein reduced the dependency of NK cells on IL-2. The amount of interferon‑γ (IFN-γ) in the supernatants of NKIL-12/Shh-C cells 5 and 7 days after transduction was significantly higher than that in the supernatants of NKIL-12 cells. Immunofluorescent staining of lung tissues from B16-bearing mice which had received an intravenous injection of lentivirus-transduced NK cells without exogenous IL-2 confirmed that donor NK cells successfully infiltrated into the lung tissues. The survival time of the mice which had received NKIL-12/Shh-C cells was significantly prolonged compared to the mice which had received NKEGFP/Shh-C cells.
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August 2012
Volume 41 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Zhu, L., Zhao, Z., Wei, Y., Marcotte , W., Wagner, T.E., & Yu, X. (2012). An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation. International Journal of Oncology, 41, 661-669. https://doi.org/10.3892/ijo.2012.1466
MLA
Zhu, L., Zhao, Z., Wei, Y., Marcotte , W., Wagner, T. E., Yu, X."An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation". International Journal of Oncology 41.2 (2012): 661-669.
Chicago
Zhu, L., Zhao, Z., Wei, Y., Marcotte , W., Wagner, T. E., Yu, X."An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation". International Journal of Oncology 41, no. 2 (2012): 661-669. https://doi.org/10.3892/ijo.2012.1466