title: Antigen-specific therapeutic approaches in Type 1 diabetes.
abstract: Development of strategies capable of specifically curbing pathogenic autoimmune responses in a disease- and organ-specific manner without impairing foreign or tumor antigen-specific immune responses represents a long sought-after goal in autoimmune disease research. Unfortunately, our current understanding of the intricate details of the different autoimmune diseases that affect mankind, including type 1 diabetes, is rudimentary. As a result, progress in the development of the so-called "antigen-specific" therapies for autoimmunity has been slow and fraught with limitations that interfere with bench-to-bedside translation. Absent or incomplete understanding of mechanisms of action and lack of adequate immunological biomarkers, for example, preclude the rational design of effective drug development programs. Here, we provide an overview of antigen-specific approaches that have been tested in preclinical models of T1D and, in some cases, human subjects. The evidence suggests that effective translation of these approaches through clinical trials and into patients will continue to meet with failure unless detailed mechanisms of action at the level of the organism are defined.
authors.affiliation: Julia McFarlane Diabetes Research Centre, University of Calgary, NW Calgary, Alberta T2N 4N1, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Clemente-Casares
authors.forename: Sue
authors.initials: S
authors.lastname: Tsai
authors.forename: Carol
authors.initials: C
authors.lastname: Huang
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
mesh_terms: D000818:Animals; D000941:Antigens / Q000627:therapeutic use*; D018834:Chaperonin 60 / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004195:Disease Models, Animal; D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D007328:Insulin / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: D000941:Antigens; D018834:Chaperonin 60; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D019444:Vaccines, DNA; D005968:Glutamate Decarboxylase