Definition

A bispecific antibody targeting both the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) and vascular endothelial growth factor A (VEGF-A), with potential immune checkpoint inhibitory, anti-angiogenic and antineoplastic activities. Upon administration, anti-PD-L1/anti-VEGF-A bispecific antibody PM8002 targets and simultaneously binds to both PD-L1 and VEGF-A expressed on tumor cells. This prevents the binding of PD-L1 to its receptor, programmed cell death protein 1 (PD-1; PDCD1; 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 tumor cells. The binding of PM8002 to VEGF-A prevents the binding of VEGF-A to VEGF receptor (VEGFR), thereby preventing the activation of VEGF-A/VEGFR-mediated signaling pathways. This prevents angiogenesis and may halt tumor cell proliferation. PD-L1 is overexpressed in many human cancer cell types and plays an important role in the downregulation of the immune system and tumor evasion from host immunity. VEGF-A is upregulated in a variety of cancer cell types and plays a crucial role in angiogenesis.