Anti-PD-1/IL-2 Bispecific Antibody Fusion Protein IBI363

**Semantic type:** Amino Acid, Peptide, or Protein|Immunologic Factor|Pharmacologic Substance

**Definition:** A bispecific antibody fusion protein composed of a monoclonal antibody targeting the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and fused to a mutated form of the endogenous cytokine interleukin-2 (IL-2), with potential immunostimulating and antineoplastic activities. Upon administration, anti-PD-1/IL-2 bispecific antibody fusion protein IBI363 targets and binds to PD-1 expressed on PD-1-expressing T-cells, thereby inhibiting PD-1-mediated signaling. This may restore immune function through the activation of T-cells and T-cell-mediated immune responses against tumor cells. IL-2 targets and binds to the IL-2 receptor IL2R and activates IL-2/IL-2R-mediated signaling, which further activates cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells, and induces expression of certain cytotoxic cytokines, such as interferon-gamma (IFNg) and transforming growth factor-beta (TGFb). This further enhances T-cell-mediated cytotoxic immune responses against tumor cells. By selectively activating PD-1 positive T-cells by IL-2, but not PD-1 negative bystander or naïve T cells, the activity of tumor specific T-cells is specifically enhanced while IL-2-induced systemic toxicity is decreased. 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.

**Synonyms:** - Anti-PD-1/IL-2 Bispecific Fusion Protein IBI363 - Fusion Protein IBI363 - IBI 363 - IBI-363 - IBI363 - PD-1/IL-2 Bispecific Molecule IBI363