Anti-NKG2A/Anti-PD-L1 Bispecific Antibody XB628

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

**Definition:** A natural killer (NK) cell engager and bispecific antibody directed against the human NK and T-lymphocyte cell checkpoint inhibitor killer cell lectin-like receptor subfamily C member 1 (KLRC1; NK group 2 member A; NKG2A) and the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with potential immunomodulating and antineoplastic activities. Upon administration, anti-NKG2A/anti-PD-L1 bispecific antibody XB628 targets and binds to NKG2A on NK cells, and PD-L1 on tumor cells. This prevents the binding of NKG2A to its ligand human leukocyte antigen-E (HLA-E), which is overexpressed on tumor cells, and blocks the HLA-E-mediated inhibition of NKG2A-positive infiltrating NKs, thereby inducing a NK-mediated cytotoxicity against the cancer cells leading to their destruction. In addition, the binding of XB628 to PD-L1 on tumor cells prevents the binding to its receptor programmed cell death protein 1 (PD-1, CD279), inhibits PD-1/PD-L1-mediated signaling, and inhibits PD-1/PD-L1-mediated downregulation of T-cell activation and proliferation. This restores and enhances a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells, thereby further killing tumor cells. Human NKG2A, an inhibitory cell surface receptor covalently bound to CD94, is expressed by NK cells and CTLs. Stimulation of the CD94/NKG2A complex inhibits the cytotoxic activity of these cells. HLA-E, a nonclassical HLA class Ib molecule, is often overexpressed on tumor cells and is associated with poor prognosis. PD-L1, which is overexpressed in many human cancer cell types, plays an important role in the downregulation of the immune system and tumor evasion from host immunity.

**Synonyms:** - Anti-PD-L1/NKG2A Bispecific Antibody XB628 - Bispecific Antibody Natural Killer Cell Engager XB628 - NK Cell Engager XB628 - PD-L1 x NKG2A Bispecific Antibody XB628 - PD-L1 x NKG2A-targeting Bispecific Antibody XB628 - XB 628 - XB-628 - XB628