دورية أكاديمية
Discovery, Function, and Therapeutic Targeting of Siglec-8.
| العنوان: | Discovery, Function, and Therapeutic Targeting of Siglec-8. |
|---|---|
| المؤلفون: | Youngblood BA; Allakos Inc., Redwood City, CA 94065, USA., Leung J; Allakos Inc., Redwood City, CA 94065, USA., Falahati R; Allakos Inc., Redwood City, CA 94065, USA., Williams J; Allakos Inc., Redwood City, CA 94065, USA., Schanin J; Allakos Inc., Redwood City, CA 94065, USA., Brock EC; Allakos Inc., Redwood City, CA 94065, USA., Singh B; Allakos Inc., Redwood City, CA 94065, USA., Chang AT; Allakos Inc., Redwood City, CA 94065, USA., O'Sullivan JA; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Schleimer RP; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Tomasevic N; Allakos Inc., Redwood City, CA 94065, USA., Bebbington CR; Allakos Inc., Redwood City, CA 94065, USA., Bochner BS; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. |
| المصدر: | Cells [Cells] 2020 Dec 24; Vol. 10 (1). Date of Electronic Publication: 2020 Dec 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
| مواضيع طبية MeSH: | Antibodies, Monoclonal, Humanized*/administration & dosage , Antibodies, Monoclonal, Humanized*/pharmacology , Antigens, CD*/immunology , Antigens, CD*/physiology , Antigens, Differentiation, B-Lymphocyte*/immunology , Antigens, Differentiation, B-Lymphocyte*/physiology , Hypersensitivity*/drug therapy , Hypersensitivity*/immunology , Inflammation*/drug therapy , Inflammation*/immunology , Lectins*/immunology , Lectins*/physiology, Eosinophils/*immunology , Mast Cells/*immunology, Animals ; Clinical Trials as Topic ; Eosinophils/pathology ; Humans ; Mast Cells/pathology ; Mice ; Mice, Transgenic |
| مستخلص: | Siglecs (sialic acid-binding immunoglobulin-like lectins) are single-pass cell surface receptors that have inhibitory activities on immune cells. Among these, Siglec-8 is a CD33-related family member selectively expressed on human mast cells and eosinophils, and at low levels on basophils. These cells can participate in inflammatory responses by releasing mediators that attract or activate other cells, contributing to the pathogenesis of allergic and non-allergic diseases. Since its discovery in 2000, initial in vitro studies have found that the engagement of Siglec-8 with a monoclonal antibody or with selective polyvalent sialoglycan ligands induced the cell death of eosinophils and inhibited mast cell degranulation. Anti-Siglec-8 antibody administration in vivo to humanized and transgenic mice selectively expressing Siglec-8 on mouse eosinophils and mast cells confirmed the in vitro findings, and identified additional anti-inflammatory effects. AK002 (lirentelimab) is a humanized non-fucosylated IgG1 antibody against Siglec-8 in clinical development for mast cell- and eosinophil-mediated diseases. AK002 administration has safely demonstrated the inhibition of mast cell activity and the depletion of eosinophils in several phase 1 and phase 2 trials. This article reviews the discovery and functions of Siglec-8, and strategies for its therapeutic targeting for the treatment of eosinophil- and mast cell-associated diseases. |
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| معلومات مُعتمدة: | P01 AI145818 United States AI NIAID NIH HHS; U19 AI136443 United States AI NIAID NIH HHS; U19 AI070535 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: AK002; Siglec-8; eosinophils; glycan ligands; lirentelimab; mast cells; monoclonal antibodies |
| المشرفين على المادة: | 0 (AK002) 0 (Antibodies, Monoclonal, Humanized) 0 (Antigens, CD) 0 (Antigens, Differentiation, B-Lymphocyte) 0 (Lectins) 0 (SIGLEC8 protein, human) |
| تواريخ الأحداث: | Date Created: 20201230 Date Completed: 20210712 Latest Revision: 20210712 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7823959 |
| DOI: | 10.3390/cells10010019 |
| PMID: | 33374255 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2073-4409 |
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| DOI: | 10.3390/cells10010019 |