Grant: Collaborative Health Research Projects (NSERC partnered)

The current proposal is founded on the discovery of a new paradigm in the treatment of type 1 diabetes (caused by the white blood cells of the immune system) of potential groundbreaking significance. Traditionally, vaccines have been used to expand white blood cells capable of affording protection against viruses, bacteria or cancer, or to delete white blood cells capable of causing autoimmune diseases (such as T1D). We have developed a 'vaccine' that can cure diabetes by selectively expanding what we call 'autoregulatory' white blood cells. These constitute a new type of 'autoreactive' white blood cells (like their diabetes-causing counterparts, they specifically recognize pancreatic ß-cells) whose function is to put the brakes on the diabetes-causing autoimmune attack. These cells become activated when they sense the attack on the pancreas and engage into a competitive tug-of-war with the ß-cell killer white blood cells, often unsuccessfully. Our vaccine can expand this population of white blood cells, enhancing their diabetes-countering effects. This vaccine can blunt disease progression in pre-diabetic animals and restore normal blood sugar levels in diabetic mice without causing generalized suppression of the immune system. The current vaccine platform is based on tiny particles of a metal (many times smaller than a cell; also referred to as nanoparticles -NP-) coated with antigenic targets of beta cell-killer white blood cells (pMHC-coated NPs). The objective of this proposal is to synthesize optimized clinical-grade pMHC-coated NPs to maximize therapeutic efficacy while reducing the potential for toxicity. This work, which will be done by an interdisciplinary team of established scientists and trainees spanning the spectrum of nanotechnology, biochemistry, immunology and autoimmune disease will pave the way for human clinical trials.