Siglec-15 is a rapidly internalised cell-surface antigen expressed by acute myeloid leukaemia cells

Siglec-15 has recently been identified as mediating a critical tumour checkpoint, augmenting the expression and function of PD-L1. We raised a monoclonal antibody, A9E8, specific for Siglec-15 using phage display. A9E8 detected cell-surface expression of Siglec-15 on myeloid blasts from both cell lines and peripheral blood cells from 9/12 AML patients. By contrast, there was minimal expression on leucocytes from healthy donors suggesting targeting Siglec-15 may have significant therapeutic advantages over its fellow Siglec CD33. After binding, A9E8 was rapidly internalized (t1/2, 180sec) into K562 cells. Antibodies to Siglec-15 hold therapeutic potential for treatment of AML.