Definition

A bispecific antibody directed against two immune checkpoint proteins composed of an engineered immunoglobulin G4 (IgG4) monoclonal antibody targeting the inhibitory receptor lymphocyte activation gene 3 protein (LAG-3; LAG3) fused with a single chain variable fragment (scFv) targeting the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-L1/anti-LAG-3 bispecific antibody ABL501 simultaneously targets and binds to LAG-3 expressed on T cells in the tumor microenvironment (TME) and PD-L1 expressed on tumor cells. This prevents LAG-3- and PD-L1-mediated signaling, reverses T-cell inactivation, activates the immune system and enhances cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune responses against PD-L1-expressing tumor cells, which together lead to a reduction in tumor growth. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding to its receptor programmed death 1 (PD-1; PDCD1; CD279) on activated T cells inhibits the expansion and survival of CD8-positive T cells, suppresses the immune system and results in immune evasion. LAG-3, a member of the immunoglobulin superfamily (IgSF), negatively regulates both the proliferation and activation of T cells. Its expression is associated with tumor-mediated immune suppression.