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 diabet...

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Bibliographic Details
Published in:Journal of the neurological sciences 2008-11, Vol.274 (1), p.9-12
Main Authors: Ochi, Hirofumi, Abraham, Michal, Ishikawa, Hiroki, Frenkel, Dan, Yang, Kaiyong, Basso, Alexandre, Wu, Henry, Chen, Mei-Ling, Gandhi, Roopali, Miller, Ariel, Maron, Ruth, Weiner, Howard L
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antibodies - administration & dosage
Antibody
Autoimmune diseases
Autoimmunity
Autoimmunity - drug effects
Autoimmunity - immunology
Biological and medical sciences
CD3 Complex - immunology
Cell surface
Cytokines
Diabetes mellitus
Diabetes Mellitus, Type 1 - therapy
Digestive tract
Encephalomyelitis, Autoimmune, Experimental - therapy
Experimental allergic encephalomyelitis
Humans
Immunological tolerance
Immunoregulation
Immunotherapy
Lymphocytes T
Medical sciences
Mice
Monoclonal antibodies
Multiple sclerosis
Neurology
Oral administration
Pneumology
Regulatory cell
Side effects
TGF-β
Transforming growth factor- beta
Transplantation
Tumors of the respiratory system and mediastinum
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Summary: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-β 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.
ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2008.07.027