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

International Journal of Oncology
Lining ZhuXianzhong Yu

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-transdu...Continue Reading

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Citations

May 23, 2020·Communications Biology·Rahul PurohitAlison E Ondrus
Jan 19, 2017·Oncology Reports·Ashlee TietjeYanzhang Wei

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