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 language | English |
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Pages (from-to) | 946-950 |
Number of pages | 5 |
Journal | British Journal of Haematology |
Volume | 193 |
Issue number | 5 |
Early online date | 5 May 2021 |
DOIs | |
Publication status | Published - 1 Jun 2021 |
Bibliographical note
AcknowledgementsThis work was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Awards in Science and Engineering (CASE) award (to Huan Cao) as well as Wellcome Trust (089821/Z/09/Z) and UK Medical Research Council (MRC) (G0901682) grants. Alexander D. Barrow was funded by a Marie Curie International Outgoing Fellowship (EC 236932). John Trowsdale received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 695551).
Keywords
- Siglec‐15
- acute myeloid leukaemia
- antibody
- phage display
- endocytosis