Biotechnology Research Centre, Pasteur Institute of Iran, Tehran, Iran; Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Biotechnology Research Centre, Pasteur Institute of Iran, Tehran, Iran.
Immunol Lett. 2019 Aug;212:106-113. doi: 10.1016/j.imlet.2019.06.009. Epub 2019 Jun 24.
Current advances in antibody engineering driving the strongest growth area in biotherapeutic agents development. Affinity improvement that is mainly important for biological activity and clinical efficacy of therapeutic antibodies, has still remained a challenging task. In the human body, during a course of immune response affinity maturation increase antibody activity by several rounds of somatic hypermutation and clonal selection in the germinal center. The final outputs are antibodies representing higher affinity and specificity against a particular antigen. In the realm of biotechnology, exploring of mutations which improve antibody affinity while preserving its specificity and stability is an extremely time-consuming and laborious process. Recent advances in computational algorithms and DNA sequencing technologies help researchers to redesign antibody structure to achieve desired properties such as improved binding affinity. In this review, we briefly described the principle of affinity maturation and different corresponding in vitro techniques. Also, we recapitulated the most recent advancements in the field of antibody affinity maturation including computational approaches and next-generation sequencing (NGS).
当前抗体工程的进展推动了生物治疗药物开发中增长最强劲的领域。亲和力的提高对于治疗性抗体的生物活性和临床疗效至关重要,但仍然是一项具有挑战性的任务。在人体中,在免疫反应的过程中,亲和力成熟通过在生发中心的体细胞超突变和克隆选择增加抗体的活性。最终的产物是针对特定抗原具有更高亲和力和特异性的抗体。在生物技术领域,探索在保持抗体特异性和稳定性的同时提高抗体亲和力的突变是一个极其耗时和费力的过程。最近计算算法和 DNA 测序技术的进步帮助研究人员重新设计抗体结构以实现所需的特性,例如提高结合亲和力。在这篇综述中,我们简要描述了亲和力成熟的原理和不同的相应体外技术。此外,我们还总结了抗体亲和力成熟领域的最新进展,包括计算方法和下一代测序(NGS)。