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

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.

Medienart:

Artikel

Erscheinungsjahr:

2005

Erschienen:

2005

Enthalten in:

Zur Gesamtaufnahme - volume:306

Enthalten in:

Journal of immunological methods - 306(2005), 1-2 vom: 30. Nov., Seite 151-60

Sprache:

Englisch

Beteiligte Personen:

Niwa, Rinpei [VerfasserIn]
Natsume, Akito [VerfasserIn]
Uehara, Aya [VerfasserIn]
Wakitani, Masako [VerfasserIn]
Iida, Shigeru [VerfasserIn]
Uchida, Kazuhisa [VerfasserIn]
Satoh, Mitsuo [VerfasserIn]
Shitara, Kenya [VerfasserIn]

Themen:

28RYY2IV3F
4F4X42SYQ6
7006-34-0
Antibodies, Monoclonal
Antibodies, Monoclonal, Murine-Derived
Antigens, CD20
Asparagine
FCGR3A protein, human
Fucose
Immunoglobulin G
Journal Article
Oligosaccharides
Receptors, IgG
Recombinant Fusion Proteins
Rituximab

Anmerkungen:

Date Completed 23.02.2006

Date Revised 02.01.2021

published: Print-Electronic

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM158294335