Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Diabetes Combination Therapy Assessment Group

Abstract

Like many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper.

Fig. 1

Pathways and opportunities to intervene in type 1 diabetes. This figure shows crucial pathways known to contribute to the pathogenesis of type 1 diabetes and relevant drugs for intervention. A key juncture is the antigen-presenting cell–T cell interaction, where activation of effector T cells can be prevented and generation of regulatory T cells (T_regs) can be enhanced. Another pivotal cell is the β cell itself. Augmentation of β cell mass or function along with prevention of apoptosis may be achievable goals. Most probably a combination of agents dampening inflammation, preventing effector cell activation, enhancing T_regs and augmenting β cell mass will be the ultimate solution for curing type 1 diabetes.