Journal
DIABETES
Volume 54, Issue 6, Pages 1763-1769Publisher
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.54.6.1763
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Funding
- NCRR NIH HHS [M01 RR000645, M01 RR001271, M01-RR-00645, M01-RR-01271] Funding Source: Medline
- NIDDK NIH HHS [R01 DK057846, P30 DK063608, P60 DK020595, R01-DK-57846, P30-DK-63608, P60-DK-20595] Funding Source: Medline
- PHS HHS [U19A146132] Funding Source: Medline
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Despite advances in understanding autoimmune diabetes in animal models, there has been little progress in altering the natural course of the human disease, which involves progression to insulin deficiency. Studies with immunosuppressive agents have shown short-term effectiveness, but they have not induced tolerance, and continuous treatment is needed. We studied the effects of hOKT3 gamma 1(Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody, on the progression of type 1 diabetes in patients with recent-onset disease in a randomized controlled trial. In general, the drug was well tolerated. A single course of treatment, within the first 6 weeks after diagnosis, preserved C-peptide responses to a mixed meal for 1 year after diagnosis (97 9.6% of response at study entry in drug-treated patients vs. 53 +/- 7.6% in control subjects, P < 0.01), with significant improvement in C-peptide responses to a mixed meal even 2 years after treatment (P < 0.02). The improved C-peptide responses were accompanied by reduced HbA(1c), and insulin requirements. Clinical responses to drug treatment were predicted by an increase in the relative number of CD8(+) T-cells in the peripheral blood after the lymphocyte count recovered 2 weeks after the last dose of drug. We conclude that treatment with the anti-CD3 monoclonal antibody hOKT3 gamma 1(Ala-Ala) results in improved C-peptide responses and clinical parameters in type 1 diabetes for at least 2 years in the absence of continued immunosuppressive medications.
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