IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides

J Immunol Methods. 2005 Nov 30;306(1-2):151-60. doi: 10.1016/j.jim.2005.08.009. Epub 2005 Sep 22.

Abstract

Fucose depletion from oligosaccharides of human IgG1-type antibodies results in a great enhancement of antibody-dependent cellular cytotoxicity (ADCC). The aim of this study was to clarify the effect of fucose removal on effector functions of all human IgG subclasses. A panel of anti-CD20 chimeric antibodies having a matched set of human heavy chain subclasses with different fucose contents in their oligosaccharides was constructed using wild-type and fucosyltransferase-knockout Chinese hamster ovary cells as host cells. As found previously for IgG1, fucose-negative variant of IgG2, IgG3, and IgG4 exhibited enhanced ADCC and FcgammaRIIIa binding compared with their highly fucosylated counterparts. In contrast, fucose removal did not affect complement-dependent cytotoxicity (CDC) of any IgGs. Consequently, fucose removal from IgG2 and IgG4 resulted in a unique effector function profile; they had potent ADCC and no CDC. In conclusion fucose depletion can provide a panel of IgGs with enhanced ADCC without an impact on other inherent properties specific for each IgG subclass, such as CDC.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal, Murine-Derived
  • Antibody-Dependent Cell Cytotoxicity*
  • Antigens, CD20 / analysis
  • Antigens, CD20 / immunology
  • Asparagine / chemistry
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Fucose / chemistry*
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / immunology*
  • Lymphoma, B-Cell / immunology
  • Oligosaccharides / chemistry*
  • Receptors, IgG / immunology
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • FCGR3A protein, human
  • Immunoglobulin G
  • Oligosaccharides
  • Receptors, IgG
  • Recombinant Fusion Proteins
  • Fucose
  • Rituximab
  • Asparagine