Randomized trial shows delayed hyperglycemia onset in NOD mice using a targeted IL-2 mutein, suggesting a new diabetes treatment approach.
Key Points
The research aims to create PSB234, an antibody-targeted immuno-cytokine, to enhance regulatory T cells and postpone hyperglycemia in Type 1 diabetes.
Developed PSB234, an IL-2 mutein with reduced receptor affinity, evaluated in vivo in NOD mice and human cells.
Mice were treated with PSB234 at 12 weeks, monitoring blood glucose and hyperglycemia incidence over 30 weeks.
Compared effects with vehicle and anti-CD3 controls.
Treatment with PSB234 resulted in only 20% incidence of diabetes in treated NOD mice compared to 46.7% in controls.
Showed a dose-dependent expansion of regulatory T cells with increased expression of GITR, ICOS, and CD25, while maintaining low levels of NK or CD8 T cell expansion.
Demonstrated significant Treg expansion, with a 20-100 fold increase in both mice and human immune cells.