New immunosuppressive approaches: oral administration of CD3-specific antibody to treat autoimmunity.
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.
Ochi
Hirofumi
H
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Abraham
Michal
M
Ishikawa
Hiroki
H
Frenkel
Dan
D
Yang
Kaiyong
K
Basso
Alexandre
A
Wu
Henry
H
Chen
Mei-Ling
ML
Gandhi
Roopali
R
Miller
Ariel
A
Maron
Ruth
R
Weiner
Howard L
HL
D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D006801:Humans; D051379:Mice
D000906:Antibodies; D017252:CD3 Complex