A genetically engineered human IgG mutant with enhanced cytolytic activity.
A mutant chimeric anti-5-dimethylaminonaphthalene-1-sulfonyl human Ig gamma that exhibited augmented effector function was constructed. Utilizing directed mutagenesis, a serine residue near the carboxyl terminus of the human IgG1 H chain (Ser444) was replaced by a cysteine. Novel intermolecular disulfide bonds between Cys444 residues linked pairs of Ig "tail-to-tail" to form covalent dimers ((H2L2)2). These dimers were 200-fold more efficient, compared with monomeric human IgG1, at antibody-dependent complement-mediated cytolysis of hapten-bearing erythrocytes. The ability to enhance the cytolytic activity of an mAb by genetic engineering may be of value in immunotherapy.
Shopes
B
B
Department of Cell Biology, Stanford University School of Medicine, CA 94305.
D000920:Antibody-Dependent Cell Cytotoxicity; D001483:Base Sequence; D002850:Chromatography, Gel; D002874:Chromosome Mapping; D003168:Complement Fixation Tests; D003165:Complement System Proteins / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D015202:Protein Engineering
D007074:Immunoglobulin G; D003165:Complement System Proteins