Oral administration of OKT3 monoclonal antibody to human subjects induces a dose-dependent immunologic effect in T cells and dendritic cells

Yaron Ilan, Ehud Zigmond, Gadi Lalazar, Adi Dembinsky, Ami Ben Ya'Acov, Nila Hemed, Ibrahim Kasis, Elizabeth Axelrod, Lidya Zolotarov, Athalia Klein, Madi El Haj, Roopali Gandhi, Claire Baecher-Allan, Henry Wu, Gopal Murugaiyan, Pia Kivisakk, Mauricio F. Farez, Francisco J. Quintana, Samia J. Khoury, Howard L. Weiner

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalJournal of Clinical Immunology
Volume30
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Funding

FundersFunder number
National Institute of Allergy and Infectious DiseasesR01AI043458
National Institute of Allergy and Infectious Diseases

    Keywords

    • Anti-CD3
    • Dendritic cells
    • IL-17
    • Immunotherapy
    • Mucosal tolerance
    • TGF-beta

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