کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5917777 1570735 2011 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel method for differentiation between Trastuzumab and host adaptive response
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Novel method for differentiation between Trastuzumab and host adaptive response
چکیده انگلیسی

Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF → SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human HER-2 ECD, we have a source of this protein to probe patient sera. Our method represents a proof of principle that mutated HER-2 which we constructed could be used to distinguish between a host response against HER-2 and the monoclonal antibody Herceptin targeting the same protein.

► We produced a mutant human HER-2 ECD that does not bind Herceptin. ► Substitution of only 3 amino acids eliminated binding. ► This protein can be a useful to discern between host adaptive response and Herceptin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 48, Issues 15–16, September 2011, Pages 1882-1885
نویسندگان
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