Definition

Fc-engineered bispecific monoclonal antibody targeting both immune checkpoint regulatory proteins human programmed death-ligand 1 (PD-L1; CD274) and 2 (PD-L2; CD273), with potential immune checkpoint inhibitory, immunostimulating and antineoplastic activities. Upon administration, anti-PD-L1/PD-L2 bispecific antibody IMGS-001 simultaneously targets and binds to PD-L1 and PD-L2 expressed on tumor cells, immunosuppressive stromal cells and endothelial cells. PD-L1 and PD-L2 binding by IMGS-001 prevents both PD-L1 and PD-L2 from binding to and activating their receptor programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1). This abrogates PD-1-mediated signaling in T cells and PD-1-mediated T-cell inhibition. This activates cytotoxic T lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which may lead to a reduction in tumor growth. In addition, IMGS-001 induces antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thereby killing PD-L1 and PD-L2-expressing cells in the tumor microenvironment (TME), and further abrogating the immunosuppressive nature of the TME. PD-L1 and PD-L2 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.