Dufner Patrick, Jermutus Lutz, Minter Ralph R
Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge CB1 6GH, UK.
Trends Biotechnol. 2006 Nov;24(11):523-9. doi: 10.1016/j.tibtech.2006.09.004. Epub 2006 Sep 26.
Therapeutic antibodies have become a major driving force for the biopharmaceutical industry; therefore, the discovery and development of safe and efficacious antibody leads have become competitive processes. Phage and ribosome display are ideal tools for the generation of such molecules and have already delivered an approved drug as well as a multitude of clinical candidates. Because they are capable of searching billions of antibody variants in tailored combinatorial libraries, they are particularly applicable to potency optimisation. In conjunction with targeted, random or semi-rational mutagenesis strategies, they deliver large panels of potent antibody leads. This review introduces the two technologies, compares them with respect to their use in antibody optimisation and highlights how they can be exploited for the successful and efficient generation of putative drug candidates.
治疗性抗体已成为生物制药行业的主要驱动力;因此,发现和开发安全有效的抗体先导物已成为竞争激烈的过程。噬菌体展示和核糖体展示是生成此类分子的理想工具,并且已经有一个获批药物以及众多临床候选药物出自这两种技术。由于它们能够在定制的组合文库中筛选数十亿种抗体变体,因此特别适用于效力优化。结合靶向、随机或半理性诱变策略,它们可提供大量强效抗体先导物。本文综述介绍了这两种技术,比较了它们在抗体优化中的应用,并强调了如何利用它们成功且高效地生成潜在药物候选物。