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Nat Rev Immunol. 2007 Aug;7(8):622-32. Epub 2007 Jul 20.

CD3-specific antibodies: a portal to the treatment of autoimmunity.

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Université René Descartes, Paris 5, Institut National de la Santé et de la Recherche Médicale, Unité 580, Hôpital Necker - Enfants Malades, 161 rue de Sèvres 75743 Paris CEDEX 15, France.


Targeted immunotherapies hold great promise for the treatment and cure of autoimmune diseases. The efficacy of CD3-specific monoclonal antibody therapy in mice and humans stems from its ability to re-establish immune homeostasis in treated individuals. This occurs through modulation of the T-cell receptor (TCR)-CD3 complex (also termed antigenic modulation) and/or induction of apoptosis of activated autoreactive T cells, which leaves behind 'space' for homeostatic reconstitution that favours selective induction, survival and expansion of adaptive regulatory T cells, which establishes long-term tolerance. This Review summarizes the pre-clinical and clinical studies of CD3-specific monoclonal antibody therapy and highlights future opportunities to enhance the efficacy of this potent immunotherapeutic.

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