TNF-alpha antagonists: monoclonal antibodies, soluble receptors, thalidomide and other novel approaches.
Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic molecule produced in response to a variety of stimuli during normal host defence. At low levels, TNF-alpha confers protection against infectious agents, tumours and tissue damage, and plays a role in the development of humoral immunity. However, overproduction of TNF-alpha has been implicated in the pathogenesis of a wide variety of conditions, including autoimmunity, malignancy, inflammatory and immunopathological diseases. Furthermore, TNF-alpha is a key regulator of other pro-inflammatory cytokines; infiltrating mononuclear cells that produce excessive amounts of TNF-alpha at sites of inflammation are, therefore, primary targets for therapeutic intervention. Traditional anti-inflammatory drugs, such as cyclosporin, have widespread immunosuppressive effects and are now being replaced by more specific anti-TNF-alpha compounds. In this report, work presented at the recent Cambridge Symposia meeting on TNF-alpha antagonists in Santa Fe, New Mexico, will be highlighted and discussed.
Division of Oncology, Department of Cellular & Molecular Sciences, St George's Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK.
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Marriott