Regulatory T cell therapy for type 1 diabetes: May the force be with you. (July 2016) - Gitelman, Stephen E.
Abstract: Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin producing beta cells. Regulatory T cells (Tregs) have been shown to be defective in this setting. Immuno-therapies targeting T cells, and resetting the balance between T effectors and Tregs, have had some initial success in preserving beta cell function. With a goal to use Tregs themselves as a novel therapeutic, we developed a technique to isolate and expand Tregs from patients with T1DM. These ex vivo expanded CD4 + CD127 lo/− CD25 + cells exhibit improved function and retain their T cell receptor diversity. These cells have subsequently been used in phase I clinical trials in patients with recent onset T1DM. The infusions were well tolerated, with no safety concerns. The studies are too small to assess efficacy definitively, although some individuals exhibit stable beta cell function over intervals as long as 2 years. These efforts set the stage for a larger phase II effort in new onset T1DM, and combination studies with other drugs, as well as efforts in other autoimmune diseases. Highlights: Type 1 diabetes results from autoimmune destruction of beta cells. Regulatory T cells (Tregs) have been shown to be defective in this setting. We developed a protocol to isolate and expand Tregs for use as a therapy. In phase 1 studies, Tregs were safe and well tolerated, with possible efficacy. Further studies are underway in diabetes and other autoimmune conditions.