[Current trends in the design and development of monoclonal antibodies against inflammatory mediators for the treatment of rheumatoid arthritis].
As mediators of inflammation, cytokines contribute significantly to both the development and the extent of the inflammatory response in rheumatoid arthritis (RA). In addition, they regulate the differentiation of various cells involved in the pathogenesis of this disease. Tumour necrosis factor alpha (TNF alpha), interleukin (IL)-1 and IL-6 constitute prominent examples of such inflammatory cytokines and have been shown to play an important role in RA. As a consequence, the use of recombinant antibodies targeting these cytokines has revolutionized the treatment of RA. However, a considerable number of RA patients do not respond adequately to therapy with such biologics. Based on this notion, this article summarizes current trends in the design and development of monoclonal antibodies against inflammatory mediators. These include the identification of alterative target structures for anti-cytokine therapies, the specific modification of the antigen-binding CDR of therapeutic antibodies to reduce immunogenicity, alterations of the Fc part and the development of modified antibody fragments to improve the pharmacokinetics and to avoid non-specific immune reactions. Beyond that, efforts are undertaken to optimize the cost of these therapies.
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Institut für Experimentelle Muskuloskelettale Medizin, Universitätsklinikum Münster, Domagkstr. 3, 48149 Münster. thomas.pap@uni-muenster.de
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001688:Biological Products / Q000627:therapeutic use*; D000068582:Certolizumab Pegol; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D015195:Drug Design; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007128:Immunoglobulin Fragments; D018836:Inflammation Mediators / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D016207:Cytokines; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D018836:Inflammation Mediators; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol