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Phage Display Libraries for Antibody Therapeutic Discovery and Development

机译:用于抗体治疗发现和开发的噬菌体展示库

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摘要

Phage display technology has played a key role in the remarkable progress of discovering and optimizing antibodies for diverse applications, particularly antibody-based drugs. This technology was initially developed by George Smith in the mid-1980s and applied by John McCafferty and Gregory Winter to antibody engineering at the beginning of 1990s. Here, we compare nine phage display antibody libraries published in the last decade, which represent the state of the art in the discovery and development of therapeutic antibodies using phage display. We first discuss the quality of the libraries and the diverse types of antibody repertoires used as substrates to build the libraries, i.e., naïve, synthetic, and semisynthetic. Second, we review the performance of the libraries in terms of the number of positive clones per panning, hit rate, affinity, and developability of the selected antibodies. Finally, we highlight current opportunities and challenges pertaining to phage display platforms and related display technologies.
机译:噬菌体展示技术在发现和优化用于多种应用的抗体(尤其是基于抗体的药物)的显着进步中发挥了关键作用。这项技术最初是由乔治·史密斯(George Smith)在1980年代中期开发的,并于1990年代初由约翰·麦卡菲蒂(John McCafferty)和格雷戈里·温特(Gregory Winter)应用于抗体工程。在这里,我们比较了过去十年发布的九种噬菌体展示抗体库,它们代表了使用噬菌体展示发现和开发治疗性抗体的最新技术。我们首先讨论文库的质量以及用作构建文库的底物的各种抗体库,即纯真,合成和半合成的。其次,我们根据每次淘选的阳性克隆数,命中率,亲和力和所选抗体的可开发性来回顾文库的性能。最后,我们重点介绍了与噬菌体展示平台和相关展示技术有关的当前机遇和挑战。

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