At the present time, biologics represent the only available class of specific TNF inhibitors available for clinical practice. Three drugs are currently approved. These are infliximab (Remicade), a chimeric monoclonal anti-TNF-a antibody comprising a human IgG-1K antibody with a mouse SV fragment of high affinity and neutralizing capacity; adalimumab (Humira), a mono clonal human antibody produced by phage display; and etanercept (Enbrel), an engineered p75 TNF receptor dimer with a fully human amino acid sequence linked to the Fc portion of human IgG-1. The monoclonal antibodies have specificity for TNF-a. Binding assays using radioactively labelled TNF- demonstrate that antibodies such as infliximab bind both monomeric (inactive) and trimeric (biologically active) forms of soluble TNF-a (Scallon et al. 2002). In contrast, the fusion protein etanercept acts as a competitive inhibitor of TNF- and can also bind lymphotoxin (TNF- ). Etanercept forms relatively unstable complexes with TNF- , allowing dissociation and the potential to form a reservoir for binding TNF-a (Scallon et al. 2002). Aside from the three currently approved biologic TNF inhibitors for rheumatoid arthritis, others are in development, including certolizumab pegol (formerly known as CDP-870, now Cimzia), a pegylated Fab fragment which can be produced in Escherichia coli (Hazle-man et al. 2000).
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