Definition

A humanized, dual antagonist monoclonal antibody directed against the inhibitory immune checkpoint receptors immunoglobulin (Ig)-like transcript 2 (ILT2; leukocyte immunoglobulin-like receptor subfamily B member 1; LILRB1; leukocyte immunoglobulin-like receptor 1; LIR1; monocyte/macrophage immunoglobulin-like receptor 7; MIR-7; CD85j) and ILT4 (LILRB2; LIR2; MIR-10; CD85d), with potential immunomodulating and antineoplastic activities. Upon administration, anti-ILT2/anti-ILT4 monoclonal antibody NGM707 targets and binds to both ILT2 and ILT4. This prevents the binding of ILT2 and ILT4 ligands, including the major histocompatibility complex class I (MHC I) molecules human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-G, to the ILT2 and ILT4 receptors and prevents ILT2- and ILT4-mediated signaling. This inhibits ILT2- and ILT4-mediated immune suppression and may activate both innate and adaptive immune responses, including natural killer (NK) and CD8+ T-cell tumor cell killing, and macrophage phagocytosis of tumor cells. ILT2 and ILT4, expressed on myeloid cells in the tumor microenvironment (TME), are upregulated in various cancer types and play an important role in tumor immune evasion. ILT2 is also expressed on various innate and adaptive immune cells including NK cells, B cells and a subset of cytolytic T cells.