New immunosuppressive approaches: oral administration of CD3-specific antibody to treat autoimmunity.

Abstract

One of the major goals for the immunotherapy of autoimmune diseases is the induction of regulatory T cells that mediate immunologic tolerance. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We have found that oral administration of anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental autoimmune encephalomyelitis both prior to disease induction and at the height of disease. Oral anti-CD3 antibody acts by inducing a unique type of regulatory T cell characterized by latency-associated peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF-beta dependent mechanism. Orally delivered antibody would not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. These findings identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions.

• Authors: Hirofumi Ochi, Michal Abraham, Hiroki Ishikawa, Dan Frenkel, Kaiyong Yang, Alexandre Basso, Henry Wu, Mei-Ling Chen, Roopali Gandhi, Ariel Miller, Ruth Maron, Howard L Weiner
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 274 Issue 1-2 Pg. 9-12 (Nov 15 2008) ISSN: 0022-510X [Print] Netherlands
• PMID: 18804221 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies
• CD3 Complex

Topics

• Administration, Oral
• Animals
• Antibodies (administration & dosage)
• Autoimmunity (drug effects, immunology)
• CD3 Complex (immunology)
• Diabetes Mellitus, Type 1 (therapy)
• Encephalomyelitis, Autoimmune, Experimental (therapy)
• Humans
• Mice