anti-PD-1/anti-PD-L1 bispecific antibody CTX-8371

A bispecific tetravalent antibody targeting both the human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and its ligand, human programmed death-ligand 1 (PD-L1; CD274), with potential checkpoint inhibitory, immunostimulating and antineoplastic activities. Upon administration, anti-PD-1/anti-PD-L1 bispecific antibody CTX-8371 simultaneously targets and binds to PD-1, which is expressed on a variety of leukocyte subsets including activated T-lymphocytes in the tumor microenvironment (TME), and PD-L1, which is expressed on tumor cells. This crosslinks PD-1-expressing T cells and PD-L1-expressing tumor cells, and prevents PD-L1 from binding to and activating its receptor PD-1, which inhibits the PD-L1/PD-1-mediated downregulation of T-cell activation and proliferation. This reverses T-cell inactivation caused by PD-L1/PD-1 signaling, increases T-cell expansion and enhances the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells. PD-L1 binding to PD-1 on activated T cells inhibits the expansion and survival of CD8-positive T cells, suppresses the immune system and results in immune evasion.