Definition

A bispecific antibody directed against both the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) and the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18), with potential immune checkpoint inhibitory, immunostimulatory and antineoplastic activities. Upon administration, anti-PD-L1/Claudin18.2 bispecific antibody Q-1802 targets and simultaneously binds to both PD-L1 and CLDN18.2 expressed on certain types of tumor cells. This prevents the binding of PD-L1 to its receptor, programmed cell death protein 1 (PD-1, CD279), inhibits the PD-1-mediated signaling, and inhibits the PD-1-mediated downregulation of T-cell activation and proliferation. This restores and enhances a cytotoxic T-lymphocyte (CTL)-mediated immune response against CLDN18.2-expressing tumor cells. 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. CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is expressed on a variety of tumor cells, but its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa.