Elimination of the immunogenicity of therapeutic antibodies.

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Gilliland LK, Walsh LA, Frewin MR, Wise MP, Tone M, Hale G, Kioussis D, Waldmann H

Elimination of the immunogenicity of therapeutic antibodies.

J Immunol. 1999 Mar 15;162(6):3663-71.

PubMed ID

10092828 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Alemtuzumab	CAMPATH-1 antigen	Protein	Humans	Yes	Antibody	Details