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Murine interleukin-12-Fc (mIL-12-Fc) is a recombinant fusion protein consisting of murine interleukin-12 (IL-12) disulfide-linked to an immunoglobulin Fc domain. IL-12 is a proinflammatory cytokine composed of p35 and p40 subunits that binds to the IL-12 receptor complex (IL-12Rβ1 and IL-12Rβ2) on T cells and natural killer (NK) cells. This binding activates the JAK-STAT signaling pathway, specifically JAK2 and TYK2, leading to STAT4 phosphorylation and the robust production of interferon-gamma (IFNγ). The Fc fusion is utilized to extend the typically short half-life of wild-type IL-12, allowing for sustained immune activation. In preclinical research, mIL-12-Fc is used as a wild-type surrogate to study IL-12-mediated anti-tumor responses and systemic toxicities, such as cytokine storms and liver inflammation, which are primarily driven by rapid NK cell activation. It serves as a benchmark for evaluating engineered IL-12 variants with improved therapeutic windows, such as partial agonists.
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