Fc糖基化与Fc蛋白工程：具有增强ADCC和CDC活性的抗体变体设计

Fc Glyco- and Fc Protein-Engineering: Design of Antibody Variants with Improved ADCC and CDC Activity.

作者信息

Kellner Christian, Derer Stefanie, Klausz Katja, Rosskopf Sophia, Wirt Tim, Rösner Thies, Otte Anna, Cappuzzello Elisa, Peipp Matthias

机构信息

Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, University Hospital Schleswig-Holstein and Christian-Albrechts, University of Kiel, Kiel, Germany.

Institute of Nutritional Medicine, Molecular Gastroenterology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

出版信息

Methods Mol Biol. 2018;1827:381-397. doi: 10.1007/978-1-4939-8648-4_20.

DOI:10.1007/978-1-4939-8648-4_20

PMID:30196508

Abstract

Monoclonal antibodies are established treatment options in cancer therapy. However, not all patients benefit from antibody therapy. Basic research and findings from clinical trials revealed that certain Fc-mediated effector mechanisms triggered by monoclonal antibodies are essential for efficient antitumor activity. Today, next-generation monoclonal antibodies can be designed displaying tailor-made improved effector functions. The introduction of Fc-engineering technologies offers the potential to fine-tune Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, or complement-dependent cytotoxicity (CDC). Fc-engineered antibodies hopefully will overcome some limitations of current forms of antibody therapy.

摘要

单克隆抗体是癌症治疗中已确立的治疗选择。然而，并非所有患者都能从抗体治疗中获益。基础研究和临床试验结果表明，单克隆抗体触发的某些Fc介导的效应机制对于有效的抗肿瘤活性至关重要。如今，可以设计出具有定制化改进效应功能的新一代单克隆抗体。Fc工程技术的引入为微调Fc介导的效应功能提供了潜力，如抗体依赖性细胞介导的细胞毒性（ADCC）、吞噬作用或补体依赖性细胞毒性（CDC）。Fc工程化抗体有望克服当前抗体治疗形式的一些局限性。