Elimination of the immunogenicity of therapeutic antibodies

The immunogenicity of therapeutic Abs limits their long-term use. The proce sses of complementarity-determining region grafting, resurfacing, and hyper chimerization 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 tolerogen ic in a number of species. If cell-binding Abs could be converted into mono meric non-cell-binding tolerogens, then it should be possible to pretoleriz e patients to the therapeutic cell-binding form, We demonstrate that non-ce ll-binding minimal mutants of the anti-CD52. Ab CAMPATH-1H lose immunogenic ity and can tolerize to the "wild-type" Ab in CD52-expressing transgenic mi ce. This finding could have utility in the long-term administration of ther apeutic proteins to humans.