MACO-355

MACO-355 is a novel, fully human, non-ligand blocking, pan-LILRB monoclonal antibody developed for the treatment of cancer. Unlike traditional LILRB-targeting antibodies that block receptor–ligand interactions to relieve immune suppression, MACO-355 does not block the interaction between LIL-receptors and MHC Class I molecules. Instead, it binds to selected members of the LILRB (Leukocyte immunoglobulin-like receptor B) family—including LILRB1, LILRB2, and LILRB3—targeting a unique membrane-proximal epitope. This mechanism enables it to mediate macrophage reprogramming under highly immunosuppressive conditions by amplifying TNFα production in macrophages and reverting M2 (TGFβ/IL-10/IL-4) macrophage-mediated suppression of T cell activity in vitro. The antibody also induces tumor cell phagocytosis and NK cell-mediated tumor killing independent of ligand status on tumor cells. Full activity requires engagement with Fc receptors and results in rewiring of the macrophage kinase network—a novel mode of action among anti-LILR therapies. Preclinical data show that MACO-355 slows tumor growth in vivo and has a favorable developability and safety profile; it is currently undergoing CMC (chemistry manufacturing controls) and IND-enabling studies[2][3][5][6][8].