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Preliminary results of early clinical trials with the fully human anti-TNFα monoclonal antibody D2E7
  1. Joachim Kempeni
  1. Department of Clinical Oncology/Immunology, Knoll AG-BASF Pharma, Knollstrasse, D-67008 Ludwigshafen, Germany
  1. Dr J Kempeni.

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Current pharmacological treatments for rheumatoid arthritis (RA), including non-steroidal anti-inflammatory drugs (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and corticosteroids, have been moderately successful in alleviating the discomforts associated with swollen, painful joints. However, conventional medical approaches to treatment have had little or no impact on the disease course of RA.1 Innovative strategies, particularly those based on new concepts in the immunobiology of RA, are being developed to target cellular inflammatory mechanisms and potentially prevent disease progression. The more promising of these treatments seem to be those that block the effects of tumour necrosis factor (TNF) α, because this proinflammatory cytokine seems to play a central part in the immunopathogenesis of RA.2 ,3

Anti-TNF treatments

Biological agents such as antibodies and soluble TNF receptors that bind TNF α with high specificity neutralise its activity and have been developed for use as therapeutic agents. Several are currently being evaluated in patients with RA (table 1). Infliximab, cA2, is a chimeric monoclonal antibody (mAb) that consists of the variable region of a murine anti-TNF mAb coupled to the constant region of human IgG1κ.4 ,5 The resulting construct is approximately two thirds human. CDP571 is a humanised mAb consisting of the complementarity determining regions of a murine anti-TNF mAb grafted into a human immunoglobulin (IgG4κ).6 This mAb is approximately 95% human. Etanercept is a fusion protein consisting of two recombinant p75 TNF receptors attached to the Fc portion of a human IgG1.7 Although this construct consists of two independent elements, which themselves contain 100% human peptide sequences, they are arranged in an unnatural configuration.

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Table 1

Anti-TNF α treatments

The duration of the therapeutic efficacy of these TNF antagonists may be limited by an immune response to their non-human elements or artificially fused human sequences. The development of antibodies to these …

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