Herold KC, Gitelman S, Greenbaum C, et al. Treatment of patients with new onset type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years

Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
Clinical Immunology (Impact Factor: 3.67). 06/2009; 132(2):166-73. DOI: 10.1016/j.clim.2009.04.007
Source: PubMed


Anti-CD3 mAbs may prolong beta cell function up to 2 years in patients with new onset Type 1 diabetes (T1DM). A randomized open label trial of anti-CD3 mAb, Teplizumab, in T1DM was stopped after 10 subjects because of increased adverse events than in a previous trial related with higher dosing of drug. Teplizumab caused transient reduction in circulating T cells, but the recovered cells were not new thymic emigrants because T cell receptor excision circles were not increased. There was a trend for reduced loss of C-peptide over 2 years with drug treatment (p=0.1), and insulin use was lower (p<0.001). In 4 drug-treated subjects followed up to 60 months, C-peptide responses were maintained. We conclude that increased doses of Teplizumab are associated with greater adverse events without improved efficacy. The drug may marginate rather than deplete T cells. C-peptide levels may remain detectable up to 5 years after treatment.

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Available from: Jeffrey Bluestone, Dec 26, 2013
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    • "Two independent clinical trials using either Teplizumab (United States) or Otelixizumab (Europe) led to the sustained preservation of insulin production. In NOD mice, anti-CD3 therapy permanently reversed diabetes and in humans C-peptide levels were sustained from 1 to 5 years, demonstrating long term protection could be obtained (Herold et al., 2002, 2009; Keymeulen et al., 2005). "
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    • "The measurements that are used actually measure β-cell function: they do not gauge the pathologic process and can be affected by metabolic factors such as ambient glucose levels. Moreover, newer immune therapies, such as FcR nonbinding anti-CD3 (teplizumab) and anti-CD20 monoclonal antibodies (rituximab) or CTLA4Ig (abatacept), have been shown to decrease the rate of decline in β-cell function, but owing to the lack of a more direct measure of β-cell destruction, their effects on the primary cause of the disease have not been assessed (3–8). As suggested by our previous studies, immune modulatory agents may cause functional recovery of degranulated β-cells even without eliminating β-cell killing (9). "
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