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 cell surface antigen CD27, with potential immune checkpoint inhibitory, immunostimulatory and antineoplastic activities. Upon administration, anti-PD-L1/CD27 bispecific antibody CDX-527 targets and binds to both PD-L1 expressed on tumor cells and CD27 expressed on a variety of immune cell types, including most T lymphocytes. 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 induces CD27-mediated signaling. This inhibits the PD-1-mediated downregulation of T-cell activation and proliferation, and enhances CD27-mediated responses, including the expansion of antigen-activated T cells and the cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. This restores immune function and activates a sustained cytotoxic T-lymphocyte (CTL)-mediated immune response against 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. CD27, a co-stimulatory molecule and member of the tumor necrosis factor receptor superfamily (TNFRSF), is expressed on T lymphocytes, memory B cells and natural killer (NK) cells. It plays an important role in NK cell-mediated cytolytic activity and T- and B-lymphocyte proliferation and activation.