Sialic acid-binding immunoglobulin-like lectin (Sigelac)-15 is a rapidly internalised cell-surface antigen expressed by acute myeloid leukaemia cells.
Huan CaoAndreas NeerincxBernard de BonoUrsula LaknerCatherine HuntingtonJohn ElvinEmma GudginClare PridansMark A VickersBrian HuntlyJohn TrowsdaleAlexander D BarrowPublished in: British journal of haematology (2021)
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.
Keyphrases
- acute myeloid leukemia
- induced apoptosis
- cell surface
- monoclonal antibody
- poor prognosis
- bone marrow
- binding protein
- dendritic cells
- cell cycle arrest
- nk cells
- allogeneic hematopoietic stem cell transplantation
- liver failure
- magnetic resonance
- pseudomonas aeruginosa
- dna binding
- endoplasmic reticulum stress
- long non coding rna
- cancer therapy
- hepatitis b virus
- low density lipoprotein
- acute respiratory distress syndrome
- drug induced