Definition

A bispecific antibody fusion protein composed of an immunoglobulin G1 (IgG1) monoclonal antibody targeting the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) and fused to anti-vascular endothelial growth factor (VEGF) protein, with potential immune checkpoint inhibitory, anti-angiogenic and antineoplastic activities. Upon administration, anti-PD-L1/anti-VEGF bispecific antibody fusion protein B1962 targets and simultaneously binds to both PD-L1 and VEGF expressed on 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 VEGF-expressing tumor cells. The binding of B1962 to VEGF prevents the binding of VEGF to its receptor VEGFR, abrogates VEGF/VEGFR-mediated signaling and may lead to the inhibition of vascular endothelial cell proliferation. The inhibition of tumor angiogenesis may further decrease tumor cell proliferation and prevent metastasis. 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 is overexpressed in a variety of cancers and is associated with increased invasiveness and decreased survival.