Immune Checkpoint‐Bioengineered Beta Cell Vaccine Reverses Early‐Onset Type 1 Diabetes

Abstract Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that results from autoreactive T cells destroying insulin‐producing pancreatic beta (β) cells. The development of T1DM is associated with the deficiency of co‐inhibitory immune checkpoint ligands (e.g., PD‐L1, CD86, and Gal‐9) in β cells. Here, a new translational approach based on metabolic glycoengineering and bioorthogonal click chemistry, which bioengineers β cells with co‐inhibitory immune checkpoint molecules that induce antigen‐specific immunotolerance and reverse early‐onset hyperglycemia is reported. To achieve this goal, a subcutaneous injectable acellular pancreatic extracellular matrix platform for localizing the bioengineered β cells while creating a pancreas‐like immunogenic microenvironment, in which the autoreactive T cells can interface with the β cells, is devised.