دورية أكاديمية
أعرض في EDS

Cell-type specific potent Wnt signaling blockade by bispecific antibody.

التفاصيل البيبلوغرافية
العنوان: Cell-type specific potent Wnt signaling blockade by bispecific antibody.
المؤلفون: Lee NK; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA., Zhang Y; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA., Su Y; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA., Bidlingmaier S; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA., Sherbenou DW; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA., Ha KD; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA., Liu B; Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA. bin.liu@ucsf.edu.
المصدر: Scientific reports [Sci Rep] 2018 Jan 15; Vol. 8 (1), pp. 766. Date of Electronic Publication: 2018 Jan 15.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Antibodies, Bispecific/*metabolism , Immunologic Factors/*metabolism , Wnt Signaling Pathway/*drug effects, Cell Line, Tumor ; Cell Proliferation/drug effects ; Humans ; Low Density Lipoprotein Receptor-Related Protein-6/metabolism ; Wnt Proteins/metabolism ; beta Catenin/metabolism
مستخلص: Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting.
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معلومات مُعتمدة: R01 CA118919 United States CA NCI NIH HHS; R01 CA129491 United States CA NCI NIH HHS; R01 CA171315 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antibodies, Bispecific)
0 (Immunologic Factors)
0 (LRP6 protein, human)
0 (Low Density Lipoprotein Receptor-Related Protein-6)
0 (Wnt Proteins)
0 (beta Catenin)
تواريخ الأحداث: Date Created: 20180117 Date Completed: 20181126 Latest Revision: 20240213
رمز التحديث: 20240213
مُعرف محوري في PubMed: PMC5768681
DOI: 10.1038/s41598-017-17539-z
PMID: 29335534
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-017-17539-z