**Part 3**

**Therapeutic Interventions** 

236 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

Triolo, G., Vadala, M., Accardo-Palumbo, A., Ferrante, A., Ciccia, F., Giardina, E., Citarrella,

antibody treatment for ocular Behcet's disease. Ann Rheum Dis *61*, 560-561. Veres, G., Baldassano, R.N., and Mamula, P. (2007). Infliximab therapy for pediatric Crohn's

Yazici, Y., Krasnokutsky, S., Barnes, J.P., Hines, P.L., Wang, J., and Rosenblatt, L. (2009).

Yokota, S., Imagawa, T., Mori, M., Miyamae, T., Aihara, Y., Takei, S., Iwata, N., Umebayashi,

blind, placebo-controlled, withdrawal phase III trial. Lancet *371*, 998-1006. Zhang, Y., Wolf-Yadlin, A., Ross, P.L., Pappin, D.J., Rush, J., Lauffenburger, D.A., and

disease. Expert Opin Biol Ther *7*, 1869-1880.

rheumatoid arthritis. J Rheumatol *36*, 907-913.

modules. Mol Cell Proteomics *4*, 1240-1250.

P., Lodato, G., and Licata, G. (2002). Anti-tumour necrosis factor monoclonal

Changing patterns of tumor necrosis factor inhibitor use in 9074 patients with

H., Murata, T., Miyoshi, M.*, et al.* (2008). Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-

White, F.M. (2005). Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic

**12** 

*Hungary* 

**Application of Monoclonal Antibody Therapies** 

Adrienn Angyal1, Jozsef Prechl2, Gyorgy Nagy3 and Gabriella Sarmay1

A better understanding of the pathogenesis of autoimmunity makes it possible to select more specific therapeutic targets and design biological agents that can replace or enhance the effect of immunosuppressive drugs; these include monoclonal antibodies, soluble receptors and molecular mimetics. This chapter aims to give a brief summary on different protein-based medications: first on the biologicals targeting cytokines that induce inflammatory responses, then on drugs depleting B cells via CD20 and CD22 and finally, on agents that inhibit cell-cell contacts and block cell survival factors. Immunogenicity of these protein preparations causes a significant problem therefore the last section gives an

Currently, there are 3 major TNF-blockers available for patients who do not react well to standard therapies like methotrexate or other disease modifying anti-rheumatic drugs (DMARDs), these are: etanercept, infliximab and adalimumab. Most common side effects of

Etanercept, a fusion protein consisting of two extracellular binding domains of the TNF receptor 2 and the Fc-part of a human IgG1 molecule is acting like a soluble decoy receptor by inhibiting ligand-binding to TNF-receptors, only with an extended in vivo half-life due to the presence of the Fc-part. It is licensed by the FDA for the treatment of RA, polyarticular juvenile idiopathic arthritis (JIA), psoritic arthritis, ankylosing spondylitis and plaque psoriasis (1). Infliximab (Remicade) is a chimeric monoclonal antibody specific for TNF that was approved by the FDA in 1998 for the treatment of Crohn's disease (2). Its use has been extended since then to the treatment of psoriasis, ankylosing spondylitis, psoriatic arthritis,

Adalimumab (Humira), another monoclonal antibody of fully human origin was derived by a phage display library and used to treat RA patients first. Since then, clinical trials proved

anti-TNF therapy are a higher susceptibility for infections and possible flares of TB.

overview of biotechnological approaches aiming to reduce this effect.

*-blocking agents (Etanercept, Adalimumab, Infliximab)* 

rheumatoid arthritis and ulcerative colitis.

**2. The blockade of cytokines inducing inflammatory responses** 

**1. Introduction** 

*TNF* **in Autoimmune Diseases** 

*at Eotvos Lorand University, Budapest,* 

*1Dept. of Immunology, Eotvos Lorand University, Budapest,* 

*3Buda Hospital of Hospitaller Brothers of St. John, Budapest* 

*2Immunology Research Group of the Hungarian Academy of Sciences,* 
