Immunotherapy in Type 1 Diabetes: A Shorter but More Winding Road?

We strive but struggle to translate immunetherapies that have been shown to be effec-tive in preclinical models of autoimmune di-abetes into use with patients. Only a small proportion of these therapies are actually tested in humans, and of these, efficacy (even short-term) has been achieved in less than a handful (1). A striking example of this struggle is provided by a clinical trial reported in the current issue of Diabetes (2). After setting everything up correctly with convincing data in preclinical models (3,4), an attractive hypothesis (5), and safety studies in animals, the Immune Tolerance Network (ITN) conducted a single-arm trial of combination therapy with interleukin (IL)-2 (4 weeks) together with rapamycin (12 weeks) in patients who had recently developed type 1 diabetes. Treatment successfully led to a respectful increase in circulating regulatory T cell (Treg) numbers. However, the therapy failed to halt b-cell loss and even transiently exacerbate