Anti-PD-1 Antibody/IL-18 Variant Immunocytokine BPT567

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

**Definition:** An immunocytokine composed of lipustobart, an antibody directed against the human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279), site-specifically conjugated to a human interleukin-18 (IL-18) variant, with potential immunostimulating and antineoplastic activities. Upon administration of anti-PD-1 antibody/IL-18 variant immunocytokine BPT567, lipustobart targets and binds to PD-1-expressing T-cells in the tumor microenvironment (TME). This prevents the activation of PD-1 and its downstream signaling pathways, leading to the activation of both T-cells and T-cell-mediated immune responses against tumor cells. The IL-18 variant binds to and activates the IL-18 receptor on the PD-1-expressing T-cells in the TME, which activates T-cells and natural killer (NK) cells and induces the secretion of interferon-gamma (IFNg). This potentiates the immune response against tumor cells. PD-1 is a transmembrane protein in the immunoglobulin (Ig) superfamily expressed on activated T-cells that negatively regulates T-cell activation and effector function when activated by its ligands. PD-1 plays an important role in tumor evasion from host immunity. IL-18 is a proinflammatory cytokine that belongs to the interleukin-1 (IL-1) superfamily of cytokines. The IL-18 variant is engineered to preferably bind to the IL-18 receptor and not IL-18 binding protein (IL-18BP), which acts as a decoy receptor of IL-18 and prevents the activation of IL-18 receptor.

**Synonyms:** - Anti-PD-1 Antibody/IL-18 Variant Fusion Protein BPT567 - Anti-PD-1 Monoclonal Antibody LZM009/IL-18 Variant Immunocytokine BPT567 - BPT 567 - BPT-567 - BPT567 - Lipustobart/IL-18 Variant Immunocytokine BPT567 - PD-1-targeting IL-18 Variant BPT567