Developing the next generation of monoclonal antibodies for the treatment of rheumatoid arthritis

被引:27
作者
Campbell, Jamie [1 ]
Lowe, David [2 ]
Sleeman, Matthew A. [1 ]
机构
[1] MedImmune Ltd, Dept Resp Inflammat & Autoimmun, Cambridge CB21 6GH, England
[2] MedImmune Ltd, Lead Generat, Cambridge CB21 6GH, England
关键词
antibody; rheumatoid arthritis; cytokine; engineering; phage display; transgenic mice; pattern recognition; toll-like receptors; biologics; NECROSIS-FACTOR-ALPHA; NEONATAL FC-RECEPTOR; TOLL-LIKE RECEPTORS; COMPLEMENTARITY-DETERMINING REGIONS; B-LYMPHOCYTE DEPLETION; DOUBLE-BLIND; SYNOVIAL TISSUE; IN-VITRO; COMBINATION THERAPY; BIOLOGICS REGISTER;
D O I
10.1111/j.1476-5381.2010.01183.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Rheumatoid arthritis is one of the commonest autoimmune diseases affecting 0.8% of the population. Over the last decade the treatment of this chronic disease has been revolutionized by the use of monoclonal antibodies and fusion proteins, targeting molecules like tumour necrosis factor alpha. Nevertheless, approximately one-third of subjects fail to respond to these therapies and therefore significant unmet medical need remains. Following a decade of use, clinical, government and regulatory agency expectations have changed for new antibodies therapies entering this highly competitive area. In this review, we discuss the current advances being made in antibody engineering and how they are being considered and used in the development of the next generation of antibodies to meet future expectations of healthcare providers, physicians and patients. Moreover, we discuss how pattern recognition receptors may provide new antibody tractable targets that may break the cycle of autoimmunity in rheumatoid arthritis.
引用
收藏
页码:1470 / 1484
页数:15
相关论文
共 130 条
[1]   Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis [J].
Abdollahi-Roodsaz, Shahla ;
Joosten, Leo A. B. ;
Koenders, Marije I. ;
Devesa, Isabel ;
Roelofs, Mieke F. ;
Radstake, Timothy R. D. J. ;
Heuvelmans-Jacobs, Marleen ;
Akira, Shizuo ;
Nicklin, Martin J. H. ;
Ribeiro-Dias, Fatima ;
Van den Berg, Wim B. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (01) :205-216
[2]   Inhibition of toll-like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis [J].
Abdollahi-Roodsaz, Shahla ;
Joosten, Leo A. B. ;
Roelofs, Mieke F. ;
Radstake, Timothy R. D. J. ;
Matera, Giovanni ;
Popa, Calin ;
van der Meer, Jos W. A. ;
Netea, Mihai G. ;
van den Berg, Wim B. .
ARTHRITIS AND RHEUMATISM, 2007, 56 (09) :2957-2967
[3]   Local Interleukin-1-Driven Joint Pathology Is Dependent on Toll-Like Receptor 4 Activation [J].
Abdollahi-Roodsaz, Shahla ;
Joosten, Leo A. B. ;
Koenders, Marije I. ;
van den Brand, Ben T. ;
van de Loo, Fons A. J. ;
van den Berg, Wim B. .
AMERICAN JOURNAL OF PATHOLOGY, 2009, 175 (05) :2004-2013
[4]   Shift From Toll-like Receptor 2 (TLR-2) Toward TLR-4 Dependency in the Erosive Stage of Chronic Streptococcal Cell Wall Arthritis Coincident With TLR-4-Mediated Interleukin-17 Production [J].
Abdollahi-Roodsaz, Shahla ;
Joosten, Leo A. B. ;
Helsen, Monique M. ;
Walgreen, Birgitte ;
van Lent, Peter L. ;
van den Bersselaar, Liduine A. ;
Koenders, Marije I. ;
van den Berg, Wim B. .
ARTHRITIS AND RHEUMATISM, 2008, 58 (12) :3753-3764
[5]   Use of pharmacokinetic/pharmacodynamic modelling for starting dose selection in first-in-human trials of high-risk biologics [J].
Agoram, Balaji M. .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2009, 67 (02) :153-160
[6]   Cutting edge: Cell surface expression and lipopolysaccharide signaling via the Toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages [J].
Akashi, S ;
Shimazu, R ;
Ogata, H ;
Nagai, Y ;
Takeda, K ;
Kimoto, M ;
Miyake, K .
JOURNAL OF IMMUNOLOGY, 2000, 164 (07) :3471-3475
[7]   IMMUNOGLOBULIN GENES IN TRANSGENIC MICE [J].
ALT, FW ;
BLACKWELL, TK ;
YANCOPOULOS, GD .
TRENDS IN GENETICS, 1985, 1 (08) :231-236
[8]   The role of HMGB1 in the pathogenesis of rheumatic disease [J].
Andersson, Ulf ;
Harris, Helena Erlandsson .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2010, 1799 (1-2) :141-148
[9]  
Bauer S, 2009, ADV EXP MED BIOL, V653, P15
[10]   Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity [J].
Boder, ET ;
Midelfort, KS ;
Wittrup, KD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (20) :10701-10705