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IL-12Fc refers to a class of recombinant fusion proteins consisting of the pro-inflammatory cytokine interleukin-12 (IL-12) linked to an immunoglobulin Fc domain, designed to extend the cytokine's half-life and enhance its therapeutic potential. A prominent example is the 'Compartment-Locked' (CL) IL-12Fc (also known as INC-101) developed by InCephalo Therapeutics. This specific variant is engineered with a silenced neonatal Fc receptor (FcRn) binding site, which 'locks' the molecule within the central nervous system (CNS) following local administration (e.g., intratumoral injection for glioblastoma). This design prevents the drug from entering systemic circulation, thereby minimizing the severe systemic toxicities—such as cytokine release syndrome and hepatotoxicity—that have historically hindered IL-12 therapy. In preclinical models, CL IL-12Fc has shown the ability to activate resident immune cells and induce a robust local interferon-gamma (IFNγ) response, leading to significant anti-tumor efficacy. Other versions, such as Hanmi Pharmaceutical's HM16390, utilize different Fc-based platforms for systemic administration in solid tumors.
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