Arslan Merve, Karadağ Dilara, Kalyoncu Sibel
İzmir Biomedicine and Genome Center , İzmir , Turkey.
İzmir Biomedicine and Genome Institute, Dokuz Eylül University , İzmir , Turkey.
Turk J Biol. 2019 Feb 7;43(1):1-12. doi: 10.3906/biy-1809-28. eCollection 2019.
The number of therapeutic antibodies in preclinical, clinical, or approved phases has been increasing exponentially, mostly due to their known successes. Development of antibody engineering methods has substantially hastened the development of therapeutic antibodies. A variety of protein engineering techniques can be applied to antibodies to improve their afinity and/or biophysical properties such as solubility and stability. Antibody fragments (where all or some parts of constant regions are eliminated while the essential antigen binding region is preserved) are more suitable for protein engineering techniques because there are many in vitro screening technologies available for antibody fragments but not full-length antibodies. Improvement of biophysical characteristics is important in the early development phase because most antibodies fail at the later stage of development and this leads to loss of resources and time. Here, we review directed evolution and rational design methods to improve antibody properties. Recent developments in rational design approaches and antibody display technologies, and especially phage display, which was recently awarded the 2018 Nobel Prize, are discussed to be used in antibody research and development.
处于临床前、临床或已获批阶段的治疗性抗体数量一直在呈指数级增长，这主要归功于其已为人所知的成功案例。抗体工程方法的发展极大地加速了治疗性抗体的研发进程。多种蛋白质工程技术可应用于抗体，以提高其亲和力和/或生物物理特性，如溶解性和稳定性。抗体片段（恒定区的全部或部分被去除，同时保留关键的抗原结合区）更适合蛋白质工程技术，因为有许多体外筛选技术可用于抗体片段，而不适用于全长抗体。在早期研发阶段改善生物物理特性非常重要，因为大多数抗体在研发后期会失败，这会导致资源和时间的浪费。在此，我们综述了用于改善抗体特性的定向进化和理性设计方法。讨论了理性设计方法和抗体展示技术，尤其是最近获得2018年诺贝尔奖的噬菌体展示技术的最新进展，这些技术可用于抗体研发。
