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

被引:160
作者
Herold, Kevan C. [1 ,2 ]
Gitelman, Stephen [3 ]
Greenbaum, Carla [7 ]
Puck, Jennifer [3 ]
Hagopian, William [8 ,9 ]
Gottlieb, Peter [10 ]
Sayre, Peter [12 ]
Bianchine, Peter [11 ]
Wong, Emelita [4 ,5 ]
Seyfert-Margolis, Vicki [12 ]
Bourcier, Kasia [12 ]
Bluestone, Jeffrey A. [6 ,12 ]
机构
[1] Yale Univ, Dept Immunobiol, New Haven, CT 06520 USA
[2] Yale Univ, Dept Med, New Haven, CT 06520 USA
[3] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Stat, San Francisco, CA 94143 USA
[5] PPD Inc, Wilmington, NC USA
[6] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[7] Benaroya Res Inst, Seattle, WA USA
[8] Pacific NW Res Inst, Dept Med, Seattle, WA USA
[9] Univ Washington, Seattle, WA 98195 USA
[10] Univ Colorado, Dept Med, Denver, CO USA
[11] Natl Inst Allergy Immunol & Infect Dis, Bethesda, MD USA
[12] Immune Tolerance Network, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
Type 1 diabetes mellitus; Immunotherapy; Anti-CD3 monoclonal antibody; T lymphocyte; T-CELL POPULATION; MONOCLONAL-ANTIBODY; THYMIC FUNCTION; OKT3; STIMULATION; ACTIVATION; APOPTOSIS; BINDING; MICE;
D O I
10.1016/j.clim.2009.04.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Anti-CD3 mAbs may prolong 1 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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:166 / 173
页数:8
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