کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2833266 1163863 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhanced binding affinity for FcγRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Enhanced binding affinity for FcγRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity
چکیده انگلیسی

Antibody-dependent cellular cytotoxicity (ADCC) is considered to be an important therapeutic function for clinical efficacy of monoclonal antibodies. Recent studies have revealed two methods to increase binding affinity for FcγRIIIa and enhance ADCC more efficiently for antibodies: (i) fucose removal from antibody N-linked complex oligosaccharides and (ii) amino acid mutations in the antibody Fc region. In this study, we compare the biological activities of the methods of generating high ADCC antibodies. We used a fucose-negative antibody and two antibodies with sets of mutations, demonstrated previously to optimally enhance ADCC using the chimeric anti-CD20 antibody, rituximab, as the model. Both amino acid mutant antibodies showed a significantly higher affinity for recombinant FcγRIIIa than fucose-negative antibody when compared using biosensor analysis. The removal of fucose from the antibodies bearing amino acid mutations exhibited a further enhancement of binding to recombinant FcγRIIIa and significantly increased binding to natural killer (NK) cells. Despite the differences manifested in binding for the FcγR, ADCCs were indistinguishable between methods and even when the methods were combined. These results indicate that the affinity of binding to FcγRIIIa does not predict ADCC beyond a certain threshold and that each method alone is sufficient to induce maximal ADCC of the antibody.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 44, Issue 12, May 2007, Pages 3122–3131
نویسندگان
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