共 22 条
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.
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页码:166 / 173
页数:8
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