CD3-specific antibodies: a portal to the treatment of autoimmunity.
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.
Chatenoud
Lucienne
L
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. chatenoud@necker.fr
Bluestone
Jeffrey A
JA
D000818:Animals; D000918:Antibody Specificity; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D011961:Receptors, Fc / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D017252:CD3 Complex; D016853:Muromonab-CD3; D011961:Receptors, Fc