Journal of Clinical Immunology

, Volume 30, Issue 1, pp 167–177

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
Article

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.

Keywords

Anti-CD3 immunotherapy mucosal tolerance dendritic cells IL-17 TGF-beta 

Supplementary material

10875_2009_9323_MOESM1_ESM.xls (67 kb)
ESM Table 1(XLS 67 KB).

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Yaron Ilan
    • 1
    • 2
  • Ehud Zigmond
    • 2
  • Gadi Lalazar
    • 2
  • Adi Dembinsky
    • 2
  • Ami Ben Ya’acov
    • 2
  • Nila Hemed
    • 2
  • Ibrahim Kasis
    • 2
  • Elizabeth Axelrod
    • 2
  • Lidya Zolotarov
    • 2
  • Athalia Klein
    • 2
  • Madi El Haj
    • 2
  • Roopali Gandhi
    • 1
  • Claire Baecher-Allan
    • 1
  • Henry Wu
    • 1
  • Gopal Murugaiyan
    • 1
  • Pia Kivisakk
    • 1
  • Mauricio F. Farez
    • 1
  • Francisco J. Quintana
    • 1
  • Samia J. Khoury
    • 1
  • Howard L. Weiner
    • 1
  1. 1.Center for Neurologic Diseases, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Department of MedicineHebrew University-Hadassah Medical CenterJerusalemIsrael

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