title: Anti-CD3 clinical trials in type 1 diabetes mellitus.
abstract: 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.
authors.affiliation: MacroGenics, Inc. 9640 Medical Center Drive, Rockville, MD 20850, USA. Electronic address: daifotisa@macrogenics.com.
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Daifotis
authors.forename: Scott
authors.initials: S
authors.lastname: Koenig
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002096:C-Peptide / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D002096:C-Peptide; D017252:CD3 Complex; D007004:Hypoglycemic Agents; D007328:Insulin; D011961:Receptors, Fc; C550701:otelixizumab; C502540:teplizumab
keywords: Anti-CD3; Otelixizumab; Teplizumab; Type 1 diabetes mellitus