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

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

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.

Keywords: ADCC; Antibody engineering; CDC.

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Antibodies / metabolism*
  • Antibody-Dependent Cell Cytotoxicity*
  • CHO Cells
  • Chromatography, Affinity
  • Complement C1q / metabolism*
  • Cricetinae
  • Cricetulus
  • Cytotoxicity, Immunologic
  • Genetic Vectors / metabolism
  • Glycosylation
  • Humans
  • Immunoglobulin Fc Fragments / metabolism*
  • Immunoglobulin G / metabolism
  • Lectins / metabolism
  • Protein Engineering / methods*
  • Receptors, IgG / metabolism

Substances

  • Antibodies
  • FCGR3A protein, human
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Lectins
  • Receptors, IgG
  • Complement C1q