Variability factors in the clinical response to recombinant antibodies and IgG Fc-containing fusion proteins.
Recombinant monoclonal antibodies and IgG Fc-containing fusion proteins represent major therapeutic advances in many diseases. However, despite their similarity with endogenous IgG, some patients respond to the treatment whilst others do not; thus raising the question of the origin of this variability. Some variability factors are now identified, of genetic origin or not, which influence either pharmacokinetics or pharmacodynamics of these drugs. Known variability factors are reviewed and classified according to their relationship with the paratope (antigen binding site) of the antibodies, with other parts of the IgGs (mostly Fc) or with IgG epitopes (antigenic motifs).
Watier
Hervé
H
Université François-Rabelais de Tours, EA 3853 IPGA (Immuno-Pharmaco-Genetics of therapeutic Antibodies), Faculté de Médecine, 37032 Tours cedex, France. watier@med.univ-tours.fr
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight; D002986:Clinical Trials as Topic; D003424:Crohn Disease / Q000378:metabolism / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics* / Q000378:metabolism; D000069285:Infliximab; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; C496124:FCGR3A protein, human; D007141:Immunoglobulin Fc Fragments; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D000069285:Infliximab