Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells
de Bono, Bernard
Vickers, Mark A.
Barrow, Alexander D.
British Journal of Haematology
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Cao, H., Neerincx, A., de Bono, B., Lakner, U., Huntington, C., Elvin, J., Gudgin, E., et al. (2021). Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells. [Other]. https://doi.org/10.1111/bjh.17496
Summary: Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 has recently been identified as a critical tumour checkpoint, augmenting the expression and function of programmed death‐ligand 1. We raised a monoclonal antibody, A9E8, specific for Siglec‐15 using phage display. A9E8 stained myeloid leukaemia cell lines and peripheral cluster of differentiation (CD)33+ blasts and CD34+ leukaemia stem cells from patients with acute myeloid leukaemia (AML). By contrast, there was minimal expression on healthy donor leucocytes or CD34+ stem cells from non‐AML donors, suggesting targeting Siglec‐15 may have significant therapeutic advantages over its fellow Siglec CD33. After binding, A9E8 was rapidly internalised (half‐life of 180 s) into K562 cells. Antibodies to Siglec‐15 therefore hold therapeutic potential for AML treatment.
Short Report, Siglec‐15, acute myeloid leukaemia, antibody, phage display, endocytosis
European Research Council (695551)
Wellcome Trust (089821/Z/09/Z)
Marie Curie International Outgoing Fellowship (EC 236932)
External DOI: https://doi.org/10.1111/bjh.17496
This record's DOI: https://doi.org/10.17863/CAM.69477