INTRODUCTION: Pathologic accumulation and activation of mast cells and 
eosinophils are implicated in allergic and inflammatory diseases. Sialic 
acid-binding immunoglobulin-like lectin (Siglec)-8 is an inhibitory receptor 
selectively expressed on mast cells, eosinophils and, at a lower extent, 
basophils. When engaged with an antibody, Siglec-8 can induce apoptosis of 
activated eosinophils and inhibit mast cell activation. AK002 is a humanized, 
non-fucosylated IgG1 anti-Siglec-8 antibody undergoing clinical investigation 
for treatment of allergic, inflammatory, and proliferative diseases. Here we 
examine the human tissue selectivity of AK002 and evaluate the in vitro, ex 
vivo, and in vivo activity of AK002 on eosinophils and mast cells.
METHODS: The affinity of AK002 for Siglec-8 and CD16 was determined by biolayer 
interferometry. Ex vivo activity of AK002 on human eosinophils from blood and 
dissociated human tissue was tested in apoptosis and antibody-dependent 
cell-mediated cytotoxicity (ADCC) assays. The in vivo activity of a murine 
precursor of AK002 (mAK002) was tested in a passive systemic anaphylaxis (PSA) 
humanized mouse model.
RESULTS: AK002 bound selectively to mast cells, eosinophils and, at a lower 
level, to basophils in human blood and tissue and not to other cell types 
examined. AK002 induced apoptosis of interleukin-5-activated blood eosinophils 
and demonstrated potent ADCC activity against blood eosinophils in the presence 
of natural killer cells. AK002 also significantly reduced eosinophils in 
dissociated human lung tissue. Furthermore, mAK002 prevented PSA in humanized 
mice through mast cell inhibition.
CONCLUSION: AK002 selectively evokes potent apoptotic and ADCC activity against 
eosinophils and prevents systemic anaphylaxis through mast cell inhibition.