کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10231461 1199 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Current methods for the synthesis of homogeneous antibody-drug conjugates
ترجمه فارسی عنوان
روش های کنونی برای سنتز کنسانتره آنتی بادی یک داروی مخدر
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی
Conventional ADCs, that employ cysteine or lysine residues as conjugation sites, are highly heterogeneous. This means that the species contain various populations of the ADCs with different drug-to-antibody ratios (DARs) and different drug load distributions. DAR and drug-load distribution are essential parameters of ADCs as they determine their stability and efficacy. Therefore, various drug-loaded forms of ADCs (usually from zero to eight conjugated molecules per antibody) may have distinct pharmacokinetics (PK) in vivo and may differ in clinical performance. Recently, a significant progress has been made in the field of site-specific conjugation which resulted in a number of strategies for synthesis of the homogeneous ADCs. This review describes newly-developed methods that ensure homogeneity of the ADCs including use of engineered reactive cysteine residues (THIOMAB), unnatural amino acids, aldehyde tags, enzymatic transglutaminase- and glycotransferase-based approaches and novel chemical methods. Furthermore, we briefly discuss the limitation of these methods emphasizing the need for further improvement in the ADC design and development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biotechnology Advances - Volume 33, Issue 6, Part 1, 1 November 2015, Pages 775-784
نویسندگان
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