Using a sophisticated nanotechnology-based “vaccine,” Canadian researchers have cured mice of type 1 diabetes-sometimes called childhood diabetes-and slowed the onset of the disease in mice at risk for the disease. The study, co-funded by the Juvenile Diabetes Research Foundation (JDRF), provides new and important insights into understanding how to stop the immune attack that causes type 1 diabetes and could even have implications for other autoimmune diseases. The study, conducted at the University of Calgary in Alberta, was published on April 8 in the online edition of the scientific journal Immunity.
The research was led by Pere Santamaria, MD, PhD, from the Julia McFarlane Diabetes Research Center (JMDRC) at the University of Calgary, Alberta. The researchers were looking specifically to stop the autoimmune response that causes type 1 diabetes without damaging the immune cells that provide protection against infections-what is called an “antigen-specific” immunotherapy. Type 1 diabetes is caused when certain white blood cells (called T cells) mistakenly attack and destroy the insulin-producing beta cells in the pancreas. “Essentially, there is an internal tug-of-war between aggressive T-cells that want to cause the disease and weaker T cells that want to stop it from occurring,” Santamaria said.
The researchers developed a unique vaccine comprised of nanoparticles, which are thousands of times smaller than the size of a cell. These nanoparticles are coated with protein fragments-peptides-specific to type 1 diabetes that are bound to molecules (MHC molecules) that play a critical role in presenting peptides to T cells. The nanoparticle vaccine worked by expanding the number of peptide-specific regulatory T cells that suppressed the aggressive immune attack that destroys beta cells. The expanded peptide-specific regulatory cells shut down the autoimmune attack by preventing aggressive autoimmune cells from being stimulated by either the peptide contained in the vaccine or by any other type-1-diabetes autoantigen presented simultaneously on the same antigen-presenting cell.
The research also provided an important insight into the ability to translate these findings in mice into therapeutics for people with diabetes: nanoparticles that contained human diabetes-relevant molecules were able to restore normal blood sugar levels in a humanized mouse model of diabetes.
According to Teodora Staeva, PhD, JDRF program director of immune therapies, a key finding from the Alberta study is that only the immune cells specifically focused on aggressively destroying beta cells (or, alternatively, regulating these cells) responded to the antigen-specific nanoparticle vaccine. That means the treatment did not compromise the rest of the immune system-a key consideration for the treatment to be safe and effective in an otherwise healthy person with type 1 diabetes.
“The potential that nanoparticle vaccine therapy holds in reversing the immune attack without generally suppressing the immune system is significant,” Staeva said. “Dr. Santamaria’s research has provided both insight into pathways for developing new immunotherapies and proof-of-concept of a specific therapy that exploits these pathways for preventing and reversing type 1 diabetes.”
Santamaria noted that the study has implications for other autoimmune diseases beyond type 1 diabetes. “If the paradigm on which this nanovaccine is based holds true in other chronic autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and others, nanovaccines might find general applicability in autoimmunity,” Santamaria said.
The nanoparticle vaccine technology used in the study is licensed by Parvus Therapeutics, Calgary, a biotechnology company focused on the development and commercialization of the nanotechnology-based therapeutics. Parvus was spun out from UTI Limited Partnership, the technology transfer and commercialization center for the University of Calgary.
