Aglycosylated chimeric mouse/human IgG1 antibody retains some effector function.
The N-linked carbohydrate attachment site of human IgG1 Ab has been eliminated by site-directed mutagenesis. Effector functions of aglycosylated Ab was then compared to its native counterpart. Aglycosylated Ab failed to exhibit any ADCC activity, but a significant level of CDC activity was retained by the aglycosylated Ab. These observations differ from those reported previously. Serum half-life and biodistribution of aglycosylated Ab in mice were comparable to the native Ab. Together, these results show that some, but not all, effector functions of a human IgG1 Ab are affected by aglycosylation.
Dorai
H
H
Abbott Biotech, Inc., Needham Heights, MA 02194.
Mueller
B M
BM
Reisfeld
R A
RA
Gillies
S D
SD
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics; D000920:Antibody-Dependent Cell Cytotoxicity; D000937:Antigen-Antibody Reactions; D001483:Base Sequence; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003165:Complement System Proteins / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics; D008546:Melanoma, Experimental / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011499:Protein Processing, Post-Translational
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D003165:Complement System Proteins