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

Huan Cao; Andreas  Neerincx; Bernard  de Bono; Ursula  Lakner; Catherine  Huntington; John  Elvin; Emma  Gudgin; Clare  Pridans; Mark Vickers; Brian  Huntly; John Trowsdale; Alexander  Barrow

doi:10.1111/bjh.17496

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 language	English
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	https://doi.org/10.1111/bjh.17496
Publication status	Published - 1 Jun 2021

Keywords

Siglec‐15
acute myeloid leukaemia
antibody
phage display
endocytosis

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Cao, H., Neerincx , A., de Bono , B., Lakner , U., Huntington , C., Elvin, J., Gudgin , E., Pridans, C., Vickers, M., Huntly, B., Trowsdale, J., & Barrow , A. (2021). Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells. British Journal of Haematology, 193(5), 946-950. https://doi.org/10.1111/bjh.17496

Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells. / Cao, Huan (Corresponding Author); Neerincx , Andreas ; de Bono , Bernard et al.

In: British Journal of Haematology, Vol. 193, No. 5, 01.06.2021, p. 946-950.

Research output: Contribution to journal › Article › peer-review

Cao, H, Neerincx , A, de Bono , B, Lakner , U, Huntington , C, Elvin, J, Gudgin , E, Pridans, C, Vickers, M, Huntly, B, Trowsdale, J & Barrow , A 2021, 'Sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐15 is a rapidly internalised cell‐surface antigen expressed by acute myeloid leukaemia cells', British Journal of Haematology, vol. 193, no. 5, pp. 946-950. https://doi.org/10.1111/bjh.17496

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

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.",

keywords = "Siglec‐15, acute myeloid leukaemia, antibody, phage display, endocytosis",

author = "Huan Cao and Andreas Neerincx and {de Bono}, Bernard and Ursula Lakner and Catherine Huntington and John Elvin and Emma Gudgin and Clare Pridans and Mark Vickers and Brian Huntly and John Trowsdale and Alexander Barrow",

note = "Acknowledgements This 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{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement No. 695551).",

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AU - Lakner , Ursula

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AU - Elvin, John

AU - Gudgin , Emma

AU - Pridans, Clare

AU - Vickers, Mark

AU - Huntly, Brian

AU - Trowsdale, John

AU - Barrow , Alexander

N1 - Acknowledgements This 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).

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N2 - 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.

AB - 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.

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

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