Definition

A tetravalent, bispecific antibody directed against both the immunosuppressive ligand programmed cell death-1 (PD-L1; cluster of differentiation 274; CD274) and the co-stimulatory receptor OX40 (CD134; TNFRSF4), with potential immune checkpoint inhibitory, immunostimulatory and antineoplastic activities. Upon administration, anti-PD-L1/anti-OX40 bispecific antibody EMB-09 binds to PD-L1 expressed on tumor cells, and simultaneously binds to and activates OX40 on activated T cells. The binding of EMB-09 to PD-L1 blocks its binding to and activation of its receptor, programmed cell death 1 (PD-1; cluster of differentiation 279; CD279). This reverses T-cell inactivation caused by PD-1/PD-L1 signaling and enhances the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells. The binding of EMB-09 to OX40 and the activation of OX40 induces the proliferation of memory and effector T lymphocytes, which also enhances the anti-tumor immune response against PD-L1-expressing tumor cells. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding to PD-1, a transmembrane protein belonging to the immunoglobulin superfamily (IgSF) that is expressed on activated T cells, suppresses the immune system and results in immune evasion. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily, is mainly expressed on activated T cells and provides a co-stimulatory signal for the proliferation and survival of activated T cells.