Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany.
Ferring Darmstadt Labs, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany.
Protein Eng Des Sel. 2020 Sep 14;33. doi: 10.1093/protein/gzaa025.
Established monoclonal antibodies (mAbs) allow treatment of cancers, autoimmune diseases and other severe illnesses. Side effects either arise due to interaction with the target protein and its biology or result from of the patient's immune system reacting to the foreign protein. This immunogenic reaction against therapeutic antibodies is dependent on various factors. The presence of non-human sequences can trigger immune responses as well as chemical and post-translational modifications of the antibody. However, even fully human antibodies can induce immune response through T cell epitopes or aggregates. In this review, we briefly describe, how therapeutic antibodies can interact with the patient's immune system and summarize recent advancements in protein engineering and in silico methods to reduce immunogenicity of therapeutic monoclonal antibodies.
已确立的单克隆抗体 (mAbs) 可用于治疗癌症、自身免疫性疾病和其他严重疾病。副作用要么是由于与靶蛋白及其生物学的相互作用引起的，要么是由于患者的免疫系统对该外来蛋白的反应引起的。这种针对治疗性抗体的免疫原性反应取决于各种因素。非人类序列的存在可以触发免疫反应，以及抗体的化学和翻译后修饰。然而，即使是完全人源化的抗体也可以通过 T 细胞表位或聚集物诱导免疫反应。在这篇综述中，我们简要描述了治疗性抗体如何与患者的免疫系统相互作用，并总结了最近在蛋白质工程和计算方法方面的进展，以降低治疗性单克隆抗体的免疫原性。
