[Monoclonal antibodies in diabetes: almost approaching the dream?]

Type 1 diabetes is characterized by the autoimmune-mediated destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. Several cells are potentially implicated in the selective destruction of beta cells, including the beta cells themselves, and T-lymphocytes and B-lymphocytes that are working as antigen-presenting cells. Both types of lymphocytes play also a role in the progressive loss of graft function after islet transplantation. Therefore, immunotherapy may represent a great opportunity to prevent, treat or even cure type 1 diabetes, and the input of monoclonal antibodies (mAb) appears crucial in such a strategy. The concept has first been validated in various animal models, especially the classical one of the NOD mouse. During recent years, promising results of a few clinical trials have been published with the administration of anti-CD3 mAbs targeting T lymphocytes at the time of diagnosis of type 1 diabetes. Results showed a more sustained residual insulin secretion during the following months associated with a reduction in insulin needs. Interesting results may also be expected from the use of anti-CD20 mAbs targeting B lymphocytes. Finally, when considering immunosuppressive therapies after beta-cell transplantation, mAbs, especially those blocking interleukin-2, are already used in clinical practice, but new trials are expected with mAbs targeting T or B lymphocytes. Thus, mAbs might be efficacious in a near future in the prevention (when administered early in the natural course of the disease, in high risk patients) and the treatment of type 1 diabetes, and therefore could avoid, or at least minimize, the constraints of intensive subcutaneous insulin therapy.