title: Oral administration of OKT3 monoclonal antibody to human subjects induces a dose-dependent immunologic effect in T cells and dendritic cells.
abstract: BACKGROUND
  Parenteral OKT3 is used to treat transplant rejection and a humanized anti-CD3 Mab has shown positive clinical effects in new onset diabetes. Oral administration of anti-CD3 has not been tested in humans, but suppresses autoimmunity in animal models. Beta-glucosylceramide enhances NKT cell and regulatory T cell activity and enhances the effects of oral anti-CD3 in animals.
  
  
  METHODS
  Fifteen healthy volunteers (three per group) received orally administered OKT3 over a dose range of 0.2 to 5.0 mg daily with or without beta-glucosylceramide 7.5 mg for 5 days. Safety and immune parameters were measured on days 5, 10, and 30.
  
  
  CONCLUSIONS
  Oral OKT3 enhanced T cell proliferation, suppressed Th1 and Th17 responses by 43% and 41%, respectively, increased TGF-beta/IL-10 expression and decreased IL-23/IL-6 expression by dendritic cells, and affected the IgG repertoire as measured by antigen arrays. Co-administration of oral beta-glucosylceramide induced similar effects. No side effects were observed and no subjects developed human anti-mouse antibodies.
  
  
  CONCLUSIONS
  These findings demonstrate that oral anti-CD3 monoclonal antibody is safe and biologically active in humans and presents a new avenue for the treatment of autoimmune diseases.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
authors.forename: Ehud
authors.initials: E
authors.lastname: Zigmond
authors.forename: Gadi
authors.initials: G
authors.lastname: Lalazar
authors.forename: Adi
authors.initials: A
authors.lastname: Dembinsky
authors.forename: Ami
authors.initials: A
authors.lastname: Ben Ya'acov
authors.forename: Nila
authors.initials: N
authors.lastname: Hemed
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Kasis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Axelrod
authors.forename: Lidya
authors.initials: L
authors.lastname: Zolotarov
authors.forename: Athalia
authors.initials: A
authors.lastname: Klein
authors.forename: Madi
authors.initials: M
authors.lastname: El Haj
authors.forename: Roopali
authors.initials: R
authors.lastname: Gandhi
authors.forename: Claire
authors.initials: C
authors.lastname: Baecher-Allan
authors.forename: Henry
authors.initials: H
authors.lastname: Wu
authors.forename: Gopal
authors.initials: G
authors.lastname: Murugaiyan
authors.forename: Pia
authors.initials: P
authors.lastname: Kivisakk
authors.forename: Mauricio F
authors.initials: MF
authors.lastname: Farez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000009:adverse effects; D000284:Administration, Oral; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005963:Glucosylceramides / Q000008:administration & dosage / Q000009:adverse effects; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007165:Immunosuppression Therapy; D008297:Male; D016853:Muromonab-CD3 / Q000008:administration & dosage* / Q000009:adverse effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000277:Adjuvants, Pharmaceutic; D000911:Antibodies, Monoclonal; D016207:Cytokines; D005963:Glucosylceramides; D007074:Immunoglobulin G; D016853:Muromonab-CD3