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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)9-12
Number of pages4
JournalJournal of the Neurological Sciences
Volume274
Issue number1-2
DOIs
StatePublished - 15 Nov 2008
Externally publishedYes

Funding

FundersFunder number
National Institute of Allergy and Infectious DiseasesR01AI043458

    Keywords

    • Antibody
    • Autoimmunity
    • Multiple sclerosis
    • Regulatory cell
    • TGF-β

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