Elimination of the Immunogenicity of Therapeutic Antibodies

Lisa K. Gilliland, Louise A. Walsh, Mark R. Frewin, Matt P. Wise, Masahide Tone, Geoff Hale, Dimitris Kioussis, Herman Waldmann
1999 Journal of Immunology  
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
more » ... ld 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.
doi:10.4049/jimmunol.162.6.3663 fatcat:gbjdr7yb3vedbegmkct7hf6zs4