Abstract

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.

Author affiliations

1. 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.
   Email: chatenoud@necker.fr
2. University of California San Francisco (UCSF) Diabetes Center, UCSF, 513 Parnassus Ave., BOX 0540, San Francisco, California 94143.
   Email: jbluest@diabetes.ucsf.edu.

Published online 20 July 2007

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