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Antibody engineering and modification technologies.

机译:抗体工程和修饰技术。

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Antibody engineering has become a well-developed discipline, encompassing discovery methods, production strategies, and modification techniques that have brought forth clinically investigated and marketed therapeutics. The realization of the long-standing goal of production of fully human monoclonal antibodies has focused intensive research on the clinical employment of this potent drug category. However, antibodies are large macromolecules that pose numerous challenges in formulation, optimal pharmacokinetics, manufacturing, stability, and process development. While further improvements in discovery technologies, such as phage display, ribosome display, and transgenic animals continue to advance our capacity to rapidly screen and refine optimal binding molecules, antibody engineers have recently focused more of their efforts on improving protein production and stability, as well as engineering improved biological properties in the effector domains of monoclonal antibodies. A second long-standing goal of antibody engineering, the development of targeted drugs, has not been wholly realized, but this obvious application for antibodies is currently undergoing increasing exploration. Minimal binding proteins, such as Fab, scFv, and single variable domains are the preferred targeting elements for some investigational drugs, whereas non-immunoglobulin scaffold proteins have been explored as binding proteins in other designs. The necessity to utilize non-protein components in targeted drugs, such as polymers, linkers, and cytotoxics, has brought a convergence of the fields of bioconjugate chemistry and protein engineering in experimental antibody therapeutics.
机译:抗体工程学已经成为一门发达的学科,涵盖了发现方法,生产策略和修饰技术,这些技术带来了临床研究和上市的治疗方法。完全人类单克隆抗体生产的长期目标的实现将集中研究集中在这种有效药物类别的临床应用上。但是,抗体是大分子,在配方,最佳药代动力学,制造,稳定性和工艺​​开发等方面均构成众多挑战。尽管发现技术的进一步改进(例如噬菌体展示,核糖体展示和转基因动物)继续提高了我们快速筛选和精炼最佳结合分子的能力,但抗体工程师最近将更多的精力集中在改善蛋白质的产生和稳定性上。作为工程改良的单克隆抗体的效应子域中的生物学特性。抗体工程的第二个长期目标,即靶向药物的开发,尚未完全实现,但是这种明显的抗体应用目前正在不断探索。最小结合蛋白(例如Fab,scFv和单个可变结构域)是某些研究药物的首选靶向元件,而非免疫球蛋白支架蛋白已在其他设计中作为结合蛋白进行了研究。在靶向药物中利用非蛋白质成分的必要性,例如聚合物,接头和细胞毒素,已使生物缀合化学和蛋白质工程领域在实验性抗体治疗中的融合。

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