PD-1 targeted IL-2 mutein fusion protein KY-0118

A fusion protein comprised of a human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279)-targeting moiety linked to an interleukin-2 (IL-2) mutein, with potential immunostimulating and antineoplastic activities. Upon administration of PD-1-targeted IL-2 mutein fusion protein KY-0118, the PD-1 targeting moiety targets and binds to PD-1 expressed on tumor-infiltrating lymphocytes (TILs) and inhibits PD-1-mediated downregulation of T-cell activation and proliferation. The IL-2 mutein moiety activates IL-2 cytokine signaling. This stimulates a local immune response and activates natural killer (NK) cells and cytotoxic T cells. This may enhance the activity of neoantigen specific T cells and potentiates T-cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands, programmed cell death-1 ligand 1 (PD-L1; B7-H1; CD274) and 2 (PD-L2); it plays an important role in tumor evasion from host immunity.