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The immunogenicity of therapeutic Abs limits their long-term use. The processes of complementarity-determining region grafting, resurfacing, and hyperchimerization diminish mAb immunogenicity by reducing the number of foreign residues. However, this does not prevent anti-idiotypic and anti-allotypic responses following repeated administration of cell-binding Abs. Classical studies have demonstrated that monomeric human IgG is profoundly tolerogenic in a number of species. If cell-binding Abs could be converted into monomeric non-cell-binding tolerogens, then it should be possible to pretolerize patients to the therapeutic cell-binding form. We demonstrate that non-cell-binding minimal mutants of the anti-CD52 Ab CAMPATH-1H lose immunogenicity and can tolerize to the "wild-type" Ab in CD52-expressing transgenic mice. This finding could have utility in the long-term administration of therapeutic proteins to humans.

Type

Journal article

Journal

J Immunol

Publication Date

15/03/1999

Volume

162

Pages

3663 - 3671

Keywords

Animals, Antibodies, Anti-Idiotypic, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm, Antigens, Binding Sites, Antibody, Cell Line, Cricetinae, Humans, Immune Tolerance, Immunoglobulin Variable Region, Injections, Intraperitoneal, Lymphocyte Depletion, Mice, Mice, Transgenic, Mutagenesis, Site-Directed, Protein Engineering, T-Lymphocytes