کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11945051 | 1081246 | 2018 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Development of a label-free FcRn-mediated transcytosis assay for in vitro characterization of FcRn interactions with therapeutic antibodies and Fc-fusion proteins
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کلمات کلیدی
FACSmAbIgGTEERFcRnb2mMDCKβ2 microglobulin - β2 میکروگلوبولینCell-based assay - آزمایش خون مبتنی بر سلولMonoclonal antibody - آنتی بادی مونوکلونالimmunoglobulin G - ایمونوگلوبولین GTranscytosis - ترانس سیتوزیسPharmacokinetics - فارماکوکینتیکmajor histocompatibility complex - مجموعه سازگاری بافتی اصلیMHC - مجموعه سازگاری بافتی اصلیTrans-epithelial electrical resistance - مقاومت الکتریکی Trans-epithelialMadin-Darby canine kidney - کلیه های سگ کوچولو Madin-Darbyneonatal Fc receptor - گیرنده Fc نوزادان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوتکنولوژی یا زیستفناوری
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The neonatal Fc receptor (FcRn) binds to the Fc domain of IgG in a pH-dependent manner, guides the intracellular movement of the bound antibodies and protects them from lysosomal degradation. Proper characterization of Fc-FcRn interactions is fundamental to successful design, development, and production of Fc-containing therapeutic proteins because of the potential impact of such interactions on their in vivo pharmacokinetic behaviors. Here, we describe the development and characterization of a cell-based, label-free FcRn-mediated transcytosis assay that provides a functional readout to reflect the totality of Fc-FcRn interactions, including pH-dependent association and dissociation, as well as the intracellular trafficking of Fc-containing molecules in complex with FcRn. Our study demonstrates that this transcytosis assay can be used to evaluate FcRn binding of therapeutic antibodies and Fc-fusion proteins, including wild-type and engineered Fc variants with varying FcRn binding affinities, as well as oxidized and aggregated antibody samples. These results support the utility of an FcRn-dependent transcytosis assay for evaluation of both Fc-FcRn interactions and the structural integrity of Fc-containing therapeutic proteins pertinent to their pharmacokinetic behavior in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Immunological Methods - Volume 462, November 2018, Pages 101-105
Journal: Journal of Immunological Methods - Volume 462, November 2018, Pages 101-105
نویسندگان
Shan Chung, Yuwen Linda Lin, Van Nguyen, Lynn Kamen, Kai Zheng, Bianca Vora, An Song,