Oral Administration of OKT3 Monoclonal Antibody to Human Subjects Induces a Dose-Dependent Immunologic Effect in T Cells and Dendritic Cells

• Published in: Journal of clinical immunology Vol. 30; no. 1; pp. 167 - 177
• Main Authors: Ilan, Yaron, Zigmond, Ehud, Lalazar, Gadi, Dembinsky, Adi, Ben Ya'acov, Ami, Hemed, Nila, Kasis, Ibrahim, Axelrod, Elizabeth, Zolotarov, Lidya, Klein, Athalia, El Haj, Madi, Gandhi, Roopali, Baecher-Allan, Claire, Wu, Henry, Murugaiyan, Gopal, Kivisakk, Pia, Farez, Mauricio F, Quintana, Francisco J, Khoury, Samia J, Weiner, Howard L
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.01.2010; Springer US; Springer Nature B.V
• Subjects: Adjuvants, Pharmaceutic - administration & dosage; Adjuvants, Pharmaceutic - adverse effects; Administration, Oral; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Autoimmune Diseases - immunology; Autoimmune Diseases - therapy; Biomedical and Life Sciences; Biomedicine; Cell Proliferation - drug effects; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Dose-Response Relationship, Immunologic; Drug Therapy, Combination; Follow-Up Studies; Glucosylceramides - administration & dosage; Glucosylceramides - adverse effects; Graft Rejection - immunology; Graft Rejection - therapy; Humans; Immunoglobulin G - blood; Immunology; Immunosuppression Therapy; Infectious Diseases; Internal Medicine; Male; Medical Microbiology; Muromonab-CD3 - administration & dosage; Muromonab-CD3 - adverse effects; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; TGF-beta; dendritic cells; mucosal tolerance; Anti-CD3; immunotherapy; IL-17
• DOI: 10.1007/s10875-009-9323-7
• ISSN: 0271-9142; 1573-2592

Introduction 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. Materials and 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. Results and discussion Oral OKT3 enhanced T cell proliferation, suppressed Th1 and Th17 responses by 43% and 41%, respectively, increased TGF-β/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. Conclusion 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.