title: Efficacy and safety of otelixizumab use in new-onset type 1 diabetes mellitus.
abstract: Type 1 diabetes (T1DM) is an immune-mediated disease induced by antigen-specific T cells infiltrating pancreatic beta cells leading to the progressive loss of endogenous insulin secretion.
  
  
  
  The identification of specific components of the autoimmune response favoured the implementation of several immunomodulatory therapies including antiCD3 monoclonal antibody (mAb) called otelixizumab. Otelixizumab is a chimeric monoclonal antibody that targets the ε-chain of the CD3T-lymphocyte surface receptor that has been developed with the aim of short therapeutic courses capable of inducing a remission of T1DM. Clinical trials have been carried out with otelixizumab to evaluate its safety and efficacy, but despite positive results of Phase I and II studies, the results of Phase III studies have been contradictory.
  
  
  
  High doses of otelixizumab have shown beneficial effects on beta cell function whereas a lower dose, which was tested to avoid the adverse effects associated with higher doses, was not effective on beta cells preservation. We believe that otelixizumab is a drug of potential interest for treating new onset T1DM patients and its use in combination with other immunomodulatory agents should be considered as a solution to circumvent adverse effects while maintaining efficacy.
authors.affiliation: a Unit of Endocrinology and Diabetes, Department of Medicine , University Campus Bio-Medico di Roma , Rome , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Guglielmi
authors.affiliation: b Centre of Immunology, Barts and The London School of Medicine and Dentistry , Queen Mary, University of London , London , UK.
authors.forename: Stefan Rhys
authors.initials: SR
authors.lastname: Williams
authors.affiliation: a Unit of Endocrinology and Diabetes, Department of Medicine , University Campus Bio-Medico di Roma , Rome , Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Del Toro
authors.affiliation: a Unit of Endocrinology and Diabetes, Department of Medicine , University Campus Bio-Medico di Roma , Rome , Italy.|b Centre of Immunology, Barts and The London School of Medicine and Dentistry , Queen Mary, University of London , London , UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007328:Insulin; C550701:otelixizumab
keywords: AntiCD3 monoclonal antibody; beta cell function; combination therapy; immunotherapy; monoclonal antibody; type 1 diabetes mellitus