کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10532562 961609 2013 25 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Altering drug tolerance of surface plasmon resonance assays for the detection of anti-drug antibodies
ترجمه فارسی عنوان
تغییر تحمل دارو از تست های رزونانس سطح پلاسما برای تشخیص آنتی بادی ضد دارو
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی
Anti-drug antibody (ADA) responses are a concern for both drug efficacy and safety, and high drug concentrations in patient samples may inhibit ADA assays. We evaluated strategies to improve drug tolerance of surface plasmon resonance (SPR) assays that detect ADAs against a bispecific Adnectin drug molecule that consists of an anti-VEGFR2 domain linked to an anti-IGF-1R domain (V-I-Adnectin). Samples containing ADAs against V-I-Adnectin and various drug concentrations were tested in the presence of 1 M guanidine hydrochloride (Gdn), at pH values ranging from 4.5 to 7.4 and temperatures of up to 37 °C. Temperature had a negligible effect in weakening the affinity of interaction of monoclonal antibodies with polyethylene glycol(PEG)-V-I-Adnectin and did not increase drug tolerance of the ADA assay. Low pH increased drug tolerance of the assay relative to pH 7.4 but caused nonspecific binding of the drug during competition experiments. The chaotropic agent Gdn lowered the affinity of interaction between an anti-V-Adnectin monoclonal antibody and the drug (from KD = 0.93 nM to KD = 348 nM). That decrease in the affinity of drug-ADA interaction correlated with an increase of assay drug tolerance. Conditions that lower drug-ADA interaction affinity could also be used to develop drug-tolerant SPR assays for other systems.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Analytical Biochemistry - Volume 441, Issue 2, 15 October 2013, Pages 174-179
نویسندگان
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