Definition

A fusion protein composed of an antibody moiety targeting the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) fused to a mutein of the immunostimulatory cytokine interleukin-15 (IL-15), with potential immune checkpoint inhibitory, immunomodulating and antineoplastic activities. Upon administration of anti-PD1/IL-15 fusion protein SAR445877, the PD-1 targeting 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-15 mutein moiety binds to the IL-15 receptor and activates IL-15-mediated signaling. This stimulates the proliferation of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and memory T cells locally in the tumor microenvironment (TME), and induces an anti-tumor immune response. This may increase tumor cell killing and decrease tumor cell proliferation. 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-15 regulates CD8+ T and NK cell development, activation and proliferation. The IL-15 mutein form lowers the systemic toxicity of IL-15.