دورية أكاديمية
أعرض في EDS

A Humanized Mouse Model Coupled with Computational Analysis Identifies Potent Glycolipid Agonist of Invariant NKT Cells.

التفاصيل البيبلوغرافية
العنوان: A Humanized Mouse Model Coupled with Computational Analysis Identifies Potent Glycolipid Agonist of Invariant NKT Cells.
المؤلفون: Saavedra-Avila NA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States., Pigni NB; Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.; Instituto de Ciencia y Tecnología de Alimentos Córdoba (ICYTAC CONICET-UNC), Ciudad Universitaria, Córdoba X5000HUA, Argentina., Caldwell DR; Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States., Chena-Becerra F; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States., Intano J Jr; Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States., Ng TW; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States., Chennamadhavuni D; Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States., Porcelli SA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States., Gascón JA; Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States., Howell AR; Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.
المصدر: ACS chemical biology [ACS Chem Biol] 2024 Apr 19; Vol. 19 (4), pp. 926-937. Date of Electronic Publication: 2024 Mar 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101282906 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8937 (Electronic) Linking ISSN: 15548929 NLM ISO Abbreviation: ACS Chem Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c2006-
مواضيع طبية MeSH: Galactosylceramides* , Glycolipids*/agonists , Natural Killer T-Cells*, Animals ; Humans ; Mice ; Antigens, CD1d
مستخلص: Invariant natural killer T (iNKT) cells play an important role in many innate and adaptive immune responses, with potential applications in cancer immunotherapy. The glycolipid KRN7000, an α-galactosylceramide, potently activates iNKT cells but has shown limited anticancer effects in human clinical trials conducted so far. In spite of almost three decades of structure-activity relationship studies, no alternative glycolipid has yet emerged as a superior clinical candidate. One reason for the slow progress in this area is that standard mouse models do not accurately reflect the specific ligand recognition by human iNKT cells and their requirements for activation. Here we evaluated a series of KRN7000 analogues using a recently developed humanized mouse model that expresses a human αTCR chain sequence and human CD1d. In this process, a more stimulatory, previously reported but largely overlooked glycolipid was identified, and its activity was probed and rationalized via molecular simulations.
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معلومات مُعتمدة: S10 OD032169 United States OD NIH HHS; R01 AI045889 United States AI NIAID NIH HHS; R01 GM111849 United States GM NIGMS NIH HHS; P30 CA013330 United States CA NCI NIH HHS; S10 OD026833 United States OD NIH HHS
المشرفين على المادة: 0 (Antigens, CD1d)
0 (Galactosylceramides)
0 (Glycolipids)
WX671898JF (KRN 7000)
تواريخ الأحداث: Date Created: 20240313 Date Completed: 20240422 Latest Revision: 20240613
رمز التحديث: 20240614
مُعرف محوري في PubMed: PMC11075374
DOI: 10.1021/acschembio.3c00736
PMID: 38477945
قاعدة البيانات: MEDLINE
الوصف
تدمد:1554-8937
DOI:10.1021/acschembio.3c00736