Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells

Huan Cao* (Corresponding Author), Andreas Neerincx , Bernard de Bono , Ursula Lakner , Catherine Huntington , John Elvin, Emma Gudgin , Clare Pridans, Mark Vickers, Brian Huntly, John Trowsdale, Alexander Barrow

*Corresponding author for this work

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Abstract

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.
Original languageEnglish
Pages (from-to)946-950
Number of pages5
JournalBritish Journal of Haematology
Volume193
Issue number5
Early online date5 May 2021
DOIs
Publication statusPublished - 1 Jun 2021

Keywords

  • Siglec‐15
  • acute myeloid leukaemia
  • antibody
  • phage display
  • endocytosis

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