What question did this study set out to answer?

The research aims to create PSB234, an antibody-targeted immuno-cytokine, to enhance regulatory T cells and postpone hyperglycemia in Type 1 diabetes.

June 7, 2026

3022-LB: An Antibody-Targeted IL-2 Mutein Expands Functionally Activated Regulatory T Cells and Delays Onset of Hyperglycemia in NOD Mice

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.

Abstract

Introduction and Objective: Deficient IL-2 signaling impairs regulatory T cell (Treg) baseline levels, functional maturity, and lineage stability, enabling autoreactive effector T cell expansion and pancreatic islet destruction in Type 1 diabetes (T1D). Our goal was to develop PSB234, a novel antibody-targeted immuno-cytokine, that could selectively expand suppressive Tregs and delay hyperglycemia onset in spontaneous T1D mice. Methods: PSB234 incorporates an IL-2 mutein with 100-fold reduced IL-2 receptor affinity in its unconjugated form. Signaling is restored to wild-type levels only upon cell-specific antibody anchoring. Treg selectivity and activation was assessed in vivo in mice and in human cells. Efficacy was evaluated in spontaneous NOD T1D mice treated at 12 weeks with a PSB234 surrogate, with vehicle and anti-CD3 as controls. Hyperglycemia incidence and blood glucose were monitored through 30 weeks. Results: Antibody-targeted delivery of our IL-2 mutein drove robust, dose-dependent Treg expansion with significantly enriched expression of GITR, ICOS, and CD25 and minimal NK or CD8 T cell expansion in vivo. In NOD mice, treatment with targeted IL-2 mutein reduced hyperglycemia incidence, with only 20% of treated mice diabetic at the end of study compared to 46.7% of vehicle and anti-CD3 treated mice. Finally, PSB234 also drove robust 20-100 fold and selective expansion of Tregs in mice with human immune cells. Conclusion: Treatment with antibody-targeted IL-2 mutein selectively amplifies suppressive Tregs and provides potent, durable delay of hyperglycemia in spontaneous NOD T1D mice. Our lead candidate molecule for PSB234 also drives robust expansion of Tregs with little to no effector immune cell expansion in mice with human immune cells. These results support the therapeutic potential of PSB234 as a precise, Treg-targeted approach to restoring and maintaining long-term immune homeostasis in Type 1 diabetes. Disclosure J.M. Kinder: None.

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