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F10 IC is an intramolecularly assembled immunocytokine (IC) designed to improve the selectivity and safety of interleukin-2 (IL-2) therapy. It consists of human IL-2 (hIL-2) genetically fused via a flexible 35-amino acid (G4S)n linker to the N-terminus of the light chain of the F10 antibody, which is an engineered variant of the anti-hIL-2 antibody MAB602. The F10 antibody component was optimized through directed evolution to bind IL-2 with high affinity and sterically occlude the binding site for the IL-2 receptor alpha subunit (IL-2Rα/CD25). By masking the IL-2Rα interface, F10 IC selectively directs IL-2 signaling toward immune effector cells (such as CD8+ T cells and NK cells) that express the IL-2Rβγ heterodimeric receptor, while minimizing the activation of immunosuppressive regulatory T cells (Tregs) that rely on the high-affinity heterotrimeric IL-2Rαβγ receptor. This biased signaling approach aims to enhance antitumor efficacy and reduce systemic toxicities, such as vascular leak syndrome, typically associated with high-dose IL-2 therapy. Developed by researchers at Johns Hopkins University, F10 IC has demonstrated potent antitumor activity in preclinical models of melanoma and colorectal cancer.
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