دورية أكاديمية
أعرض في EDS

Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells.

التفاصيل البيبلوغرافية
العنوان: Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells.
المؤلفون: Schanin J; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Korver W; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Brock EC; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Leung J; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Benet Z; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Luu T; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Chang K; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Xu A; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., De Freitas N; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Luehrsen K; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Brehm MA; University of Massachusetts Medical School, Worcester, MA, USA., Wong A; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA., Youngblood BA; Allakos, Inc., 825 Industrial Rd Suite, 500, San Carlos, CA, USA. byoungblood@allakos.com.
المصدر: Communications biology [Commun Biol] 2022 Nov 11; Vol. 5 (1), pp. 1226. Date of Electronic Publication: 2022 Nov 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
مواضيع طبية MeSH: Mast Cells* , Antigens, CD*/chemistry, Humans ; Mice ; Animals ; Sialic Acid Binding Immunoglobulin-like Lectins ; Antibodies, Monoclonal/pharmacology ; Epitopes
مستخلص: Mast cells (MC) are key drivers of allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 is an immunoregulatory receptor found on MCs. While it is recognized that engaging Siglecs with antibodies mediates inhibition across immune cells, the mechanisms that govern this agonism are not understood. Here we generated Siglec-6 mAb clones (AK01 to AK18) to better understand Siglec-6-mediated agonism. Siglec-6 mAbs displayed epitope-dependent receptor internalization and inhibitory activity. We identified a Siglec-6 mAb (AK04) that required Fc-mediated interaction for receptor internalization and induced inhibition and antibody-dependent cellular phagocytosis against MCs. AK04-mediated MC inhibition required Siglec-6 immunoreceptor tyrosine-based inhibitory motif (ITIM) and ITIM-like domains and was associated with receptor cluster formation containing inhibitory phosphatases. Treatment of humanized mice with AK04 inhibited systemic anaphylaxis with a single dose and reduced MCs with chronic dosing. Our findings suggest Siglec-6 activity is epitope dependent and highlight an agonistic Siglec-6 mAb as a potential therapeutic approach in allergic disease.
(© 2022. The Author(s).)
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المشرفين على المادة: 0 (Antigens, CD)
0 (Sialic Acid Binding Immunoglobulin-like Lectins)
0 (Antibodies, Monoclonal)
0 (Epitopes)
تواريخ الأحداث: Date Created: 20221112 Date Completed: 20221115 Latest Revision: 20221220
رمز التحديث: 20221221
مُعرف محوري في PubMed: PMC9652399
DOI: 10.1038/s42003-022-04207-w
PMID: 36369358
قاعدة البيانات: MEDLINE
الوصف
تدمد:2399-3642
DOI:10.1038/s42003-022-04207-w