anti-PD-1/anti-PD-L1 bispecific antibody IBI318

A recombinant immunoglobulin G1 (IgG1) bispecific 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 IBI318 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. This prevents PD-L1 from binding to and activating its receptor PD-1 and inhibits the PD-L1/PD-1-mediated downregulation of T-cell activation and proliferation. This abrogates T-cell inhibition, activates antigen-specific T lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which may lead to a reduction in tumor growth. 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.