AMV564 is a homodimer that forms four single chain variable fragments (scFvs) which bind CD33 on myeloid cells and CD3 epsilon on the T cell receptor. Ternary complexes produce an immune synapse that leads to T cell-directed lysis of target cells.
CD33 is highly expressed on MDSC and leukemic blasts. Upon activation, CD33 relocalizes to glycolipid-enriched domains (lipid rafts). An important ligand for CD33 is the sialoglycan S100A9, which promotes expansion and production of immune-suppressive cytokines and factors by MDSC via CD33 engagement (1).
The selectivity of AMV564 is driven by avid binding to cells where CD33 is highly expressed and clustered in an activated configuration, such as in leukemic blasts and MDSC.