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IL-2-TGF-β surrogate agonist
- Development stage
- Preclinical
- Lead developer
- Stanford University
- Modality
- Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes
- Administration
- Intperitoneal, Intravenous
01
Overview
The IL-2-TGF-beta surrogate agonist is a single-chain recombinant fusion protein designed to induce peripheral regulatory T cells (pTregs) and establish immune tolerance. Developed by researchers at Stanford University, the molecule is an AND-gated co-agonist that fuses interleukin-2 (IL-2) with a low-affinity TGF-beta mimic agonist derived from a helminth parasite. This design enables simultaneous cis-activation of both IL-2-STAT5 and TGF-beta-SMAD2/3 signaling specifically in T cells expressing IL-2 receptors. In preclinical mouse models, the agonist robustly induced antigen-specific, functional, and stable pTregs, effectively suppressing allergen-induced allergic inflammation and self-antigen-driven autoimmune neuroinflammation.
- Other names
- IL-2-TGF-beta surrogate agonistIL2-TGF-beta surrogate agonistIL 2-TGF-beta surrogate agonistInterleukin-2-TGF-beta surrogate agonistInterleukin2-TGF-beta surrogate agonistInterleukin 2-TGF-beta surrogate agonistInterleukin-2-TGF-β surrogate agonist
02
Targets
IL-2RA (Interleukin-2 receptor subunit alpha)IL2RB (IL-2 receptor beta chain)SMAD2 (Mothers against decapentaplegic homolog 2)STAT5A (STAT5)TGFBR1IL2RG (Interleukin-2 receptor gamma subunit)TGFBR2 (TGF-β receptor type 2)
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