Definition

An antibody directed against the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) fused to a mutein of the cytokine interleukin-21 (IL-21), with potential immune checkpoint inhibitory, immunomodulating and antineoplastic activities. Upon administration of anti-PD-1 antibody-IL-21 mutein fusion protein AMG 256, the antibody moiety specifically targets, binds to and inhibits PD-1 and its downstream signaling pathways. This may restore immune function through the activation of T cells and T-cell-mediated immune responses against tumor cells. The IL-21 mutein moiety binds to the IL-21 receptor and activates IL-21 cytokine signaling in PD-1-expressing cells. This may modulate the proliferation and/or differentiation, promote survival, and increase the cytolytic activity of PD-1-expressing T cells, thereby enhancing 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; cluster of differentiation 274; CD274) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity. IL-21 plays an important role in the regulation of cellular immune responses.