Definition

A recombinant humanized bispecific antibody directed against the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and the human vascular endothelial growth factor (VEGF), with potential immune checkpoint inhibitory, anti-angiogenic and antineoplastic activities. Upon administration, anti-PD-1/anti-VEGF bispecific antibody JS207 simultaneously targets and binds to both PD-1 expressed on T cells and VEGF expressed on tumor cells. The binding of JS207 to PD-1 prevents the activation of PD-1 by its ligands, programmed cell death-1 ligand 1 (PD-L1; CD274) and/or 2 (PD-L2; CD273). This abrogates T-cell inhibition, activates antigen-specific T lymphocytes and enhances cytotoxic T-lymphocyte (CTL)-mediated tumor cell lysis, which may lead to a reduction in tumor growth. The binding of JS207 to VEGF prevents 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-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands PD-L1 and/or PD-L2; it plays an important role in tumor evasion from host immunity. VEGF is overexpressed in a variety of cancers and is associated with increased invasiveness and decreased survival.