Autoantigen-specific adoptive regulatory T cell therapy against type 1 diabetes (ARTiDe)

Type 1 diabetes (T1D) is an incurable disease, often starting in childhood, with a risk of devastating complications, premature mortality, and high social burden. It is caused by the autoimmune destruction of insulin-producing beta cells, yet the standard of care is insulin replacement, acting only at the symptom level. Thus, T1D is a disease with a high unmet need for innovative therapy. Ideally, such therapy shall suppress selectively the immune cells driving T1D without impairing protective immunity. Regulatory T cells (Tregs) are the guardians of human immune tolerance, and genetic defects in Tregs are associated with T1D. Tregs additionally possess tissue regenerative capacity, making them ideal to treat T1D in cell therapy. However, such therapy, performed with polyclonally expanded patient Tregs, showed limited efficacy in T1D. These expanded Tregs are however poor in relevant autoreactive Tregs to save insulin-producing cells. In fact, the identification and manufacturing of autoreactive Tregs remain fundamental technical challenges to successfully apply these cells in the clinic. ARTiDe aims at a breakthrough in antigen-specific Treg therapy in T1D by establishing the production of human Tregs genetically engineered to express an autoreactive T cell antigen receptor (TCR) ready for clinical use. To achieve this ambitious goal, ARTiDe combines the complementary expertise of 8 partners providing novel technologies for the systematic identification of autoantigen-specific Tregs in humans, the selection of optimal TCR to produce protective Tregs, and innovative humanized T1D pre-clinical models to test their efficacy and safety, as well as Treg supporting strategies, in vivo. World-leading biotechs for adoptive T cell therapy will establish novel GMP-compatible manufacturing of highly purified TCR-engineered Tregs. ARTiDe will deliver a Treg production process and regulatory certificates that will allow launching a phase 1 clinical trial just after the project.