Anti-CD3 clinical trials in type 1 diabetes mellitus

Clin Immunol. 2013 Dec;149(3):268-78. doi: 10.1016/j.clim.2013.05.001. Epub 2013 May 11.


Two humanized, anti-CD3 mAbs with reduced FcR binding, teplizumab and otelixizumab, have been evaluated in over 1500 subjects, ages 7-45, with new and recently diagnosed T1D with a range of intravenous doses (3-48mg) and regimens (6-14 days, single or repeat courses). In general, studies that used adequate dosing demonstrated improvement in stimulated C-peptide responses and reduced need for exogenous insulin for two years and even longer after diagnosis. Drug treatment causes a transient reduction in circulating T cells, but the available data suggest that the mechanism of action may involve induction of regulatory mechanisms. The adverse effects of anti-CD3 treatment are infusion-related and transient. The studies have identified significant differences in efficacy among patient groups suggesting that a key aspect for development of this immune therapy is identification of the demographic, metabolic, and immunologic features that distinguish subjects who are most likely to show beneficial clinical responses.

Keywords: Anti-CD3; Otelixizumab; Teplizumab; Type 1 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • C-Peptide / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism*
  • Child
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Infusions, Intravenous
  • Insulin / metabolism
  • Male
  • Middle Aged
  • Receptors, Fc / immunology
  • Receptors, Fc / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology


  • Antibodies, Monoclonal, Humanized
  • C-Peptide
  • CD3 Complex
  • Hypoglycemic Agents
  • Insulin
  • Receptors, Fc
  • otelixizumab
  • teplizumab