ArticleInternational archives of allergy and immunology2019
AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice.
Article in International archives of allergy and immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 107 citations in OpenAlex.
- Benralizumab Completely Depletes Gastrointestinal Tissue Eosinophils and Improves Symptoms in Eosinophilic Gastrointestinal Disease.The journal of allergy and clinical immunology. In practice · 2022Trial
- Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis.The New England journal of medicine · 2020Trial
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Emerging Therapies for Anaphylaxis.Immunology and allergy clinics of North America · 2026Review
- Investigational Approaches in Treatment of Nonadvanced Mastocytosis.Current allergy and asthma reports · 2026Review
- [Advances in targeted therapies for chronic spontaneous urticaria].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- The Immune Architecture of Eosinophilic Esophagitis: Mechanisms, Therapeutic Targets, and Precision Management.ImmunoTargets and therapy · 2026Review
- Exploring Siglecs: Potential Modulators of Immune Cells in Food Allergy and Therapeutic Applications.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025Review
- Hereditary alpha tryptasemia and clinical implications.World journal of clinical cases · 2025Review
- Engrafted NSG-SGM3 humanized mice spontaneously produce human immunoglobulins including IgE.Frontiers in immunology · 2025Article
- Caffeine Acts as an Agonist of Siglec-6, Inhibits MRGPRX2-Triggered Mast Cell Degranulation and Anaphylactoid Reactions.Mediators of inflammation · 2025Article
- Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways.Immunological reviews · 2024Review
- Article
- From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis.Biomolecules · 2024Review
- Mast cells: a novel therapeutic avenue for cardiovascular diseases?Cardiovascular research · 2024Review
- The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review.Diagnostics (Basel, Switzerland) · 2024Review
- Engineering therapeutic monoclonal antibodies.The Journal of allergy and clinical immunology · 2024Review
- The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs.International journal of molecular sciences · 2024Review
- Vectorized Human Antibody-Mediated Anti-Eosinophil Gene Therapy.Human gene therapy · 2024Article
- Current and Novel Therapies for Eosinophilic Gastrointestinal Diseases.International journal of molecular sciences · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
introductionPathologic 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.
methodsThe 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.
resultsAK002 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.
conclusionAK002 selectively evokes potent apoptotic and ADCC activity against eosinophils and prevents systemic anaphylaxis through mast cell inhibition.
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Registered trials
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