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Clec9A-AcTaferon is a preclinical-stage recombinant fusion protein designed to deliver targeted type I interferon activity to the tumor microenvironment. It consists of a VHH single-domain antibody (nanobody) specific for Clec9A (DNGR-1), a receptor exclusively expressed on type 1 conventional dendritic cells (cDC1s), fused to an "AcTaferon" (AFN)—a mutated, attenuated version of human interferon alpha 2 (IFN-α2, typically the Q124R mutant). By targeting cDC1s, the drug aims to activate the innate and adaptive immune systems within the tumor while minimizing the systemic toxicities (such as hematological side effects and weight loss) associated with wild-type interferon therapy. Preclinical studies in murine models of melanoma, breast cancer, and lymphoma have demonstrated its ability to promote pro-immunogenic macrophage and neutrophil profiles, enhance cDC1 maturation, and diversify the CD8+ T cell repertoire, particularly when used in combination with checkpoint inhibitors like anti-PD-L1.
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