Tregs as Vehicles for Targeted Delivery of Therapeutic Payload to Human Islets
Contact PI: Qizhi Tang, PhD, University of California, San Francisco
Start Date: September 2022
HIRN Catalyst Award Recipient
Regulatory T cells (Tregs) are vital to immune self-tolerance and their deficiencies result in autoimmune diseases including T1D. Islet antigen specific Tregs infused in NOD mice traffic to pancreatic islets to suppress immune aggression against beta cells thus effectively treat the disease. Early-phase clinical trials of Treg therapy in patients with T1D have shown that it is feasible and safe, and ongoing research is developing islet antigen specific Tregs to better target pancreatic islets. Here, we propose to explore the idea of using Tregs to deliver anti-inflammatory and beta cell-tropic agents to the pancreatic islets as an approach to tailor Tregs to counteract the pathophysiology of T1D. Compared to other payload-delivery approaches, Tregs have the advantages of capable of trafficking, proliferating, and accumulating in the islets, being long-lived, and having basal anti-inflammatory properties; thus, they are attractive candidate for targeted delivery of therapeutics. Work proposed in this catalyst award will construct an islet-induced payload delivery system, express it in human Tregs, and test the delivery of a few selected payloads to human islets transplanted in NSG mice.