“
“Immune-based therapies that prevent type 1 diabetes or preserve metabolic function remaining at diagnosis have become a major objective for funding agencies and international trial consortia, and receive backing from notable patient advocate groups. The development of immune-based therapeutic strategies in this arena requires a careful balancing of the risks of the therapy

against the potential benefits, because many individuals are diagnosed or identified as being at increased risk of disease in early childhood, a period when manipulation of the developing immune system should be undertaken with caution. In addition, a therapy exists (daily insulin injection) that is life-saving in the acute stages of disease and can be used effectively MK-1775 manufacturer over Gemcitabine a lifetime as maintenance. Conversely, the disease is increasing in incidence; is peaking in ever-younger age groups; carries significant risk of increased

morbidity and early mortality; and remains difficult to manage effectively in many settings. With these issues in mind, in this article we review progress towards immune-based strategies for this chronic autoimmune disease. Other Articles Published in this Series Immunological biomarkers: Catalysts for translational advances in autoimmune diabetes. Clinical and Experimental Immunology 2013, 172: 178–85. With the exception of one or two early attempts at disease modulation, the field of immunotherapy for type 1 diabetes did not develop significant DOK2 momentum until the 1980s, during which a series of studies were initiated that made use of a drug (cyclosporin) which had, by then, revolutionized immune

suppression in the setting of organ transplantation. Some 20 years on from those early successes, in 2007 we reviewed the status of intervention and prevention trials for type 1 diabetes [1]. The timing of our commentary was significant; the first major advance since cyclosporin had recently emerged, notably with the publication of two studies using monoclonal antibodies (mAbs) targeting CD3 and engineered to have limited Fc binding, both of which demonstrated clinically relevant efficacy with manageable toxicity [2, 3]. At that stage we discussed the fact that these drugs (subsequently emerging as teplizumab and otelixizumab) were lead agents at the head of a therapeutic pipeline of immunomodulators. These included several drugs that were emerging from the fields of transplantation immunology and as treatments for other autoimmune and inflammatory diseases, as well as disease-specific, antigen-based therapeutics.