Researchers from The Institute, in collaboration with Sanofi, develop a novel therapy to enhance immune regulation in type 1 diabetes
In a groundbreaking new study, scientists from the Research Institute of the McGill University Health Centre (The Institute) have engineered a novel interleukin-2 (IL-2) molecule, named IL-2 SYNTHORIN, that shows promise in treating autoimmune diseases such as type 1 diabetes. Recently published in JCI Insight, the study was led by Ciriaco Piccirillo, PhD, of the Infectious Diseases and Immunity in Global Health (IDIGH) Program at The Institute, in collaboration with Sanofi-Aventis, one of Europe’s largest pharmaceutical firms. Their findings reveal that IL-2 SYNTHORIN can bolster natural immune regulation by promoting the growth of regulatory T cells (Tregs), which play a crucial role in maintaining immune balance.
Autoimmune diseases occur when the immune system mistakenly attacks the body’s own tissues. In type 1 diabetes, this leads to the destruction of insulin-producing cells in the pancreas. Traditional IL-2 therapies have been limited in their effectiveness because they activate a broad range of immune cells, potentially triggering harmful inflammation. The newly engineered IL-2 SYNTHORIN molecule overcomes this challenge by preferentially binding to the IL-2 receptor alpha chain (CD25), thereby selectively expanding Tregs without stimulating pro-inflammatory cells.
In preclinical models of type 1 diabetes, administration of IL-2 SYNTHORIN resulted in a significant increase in Treg populations within the pancreas. This expansion of Tregs was associated with a decrease in insulitis—an inflammatory process that damages insulin-producing islets—indicating a protective effect against the autoimmune attack that drives the disease. Notably, IL-2 SYNTHORIN also promoted the differentiation of Tregs into specialized subsets capable of producing IL-10, an anti-inflammatory cytokine that further supports immune regulation.
Prof. Piccirillo, senior author of the study and a leading expert in regulatory T cell biology highlighted the potential impact of this discovery: “By selectively expanding regulatory T cells, IL-2 SYNTHORIN offers a promising therapeutic avenue for autoimmune diseases like type 1 diabetes.”
The development of IL-2 SYNTHORIN represents a collaborative effort between The Institute and Sanofi, combining academic research and pharmaceutical innovation.
“The next steps involve advancing this therapy into human clinical trials to assess its safety and efficacy in patients with autoimmune diseases,” adds Prof. Piccirillo.
This research was funded by the Canadian Institutes of Health Research (CIHR) and benefited from the expertise of The Institute’s Immunophenotyping Platform.
About the study
The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes. Fernando Alvarez, Nicole V. Acuff, Glenn M. La Muraglia II, Nazila Sabri, Marcos E. Milla, Jill M. Mooney, Matthew F. Mackey, Mark Peakman, and Ciriaco A. Piccirillo. JCI Insight. 2024 9(24).