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Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.
- Source :
- BioDrugs; Mar2024, Vol. 38 Issue 2, p227-248, 22p
- Publication Year :
- 2024
-
Abstract
- The interleukin-2 (IL-2) cytokine plays a crucial role in regulating immune responses and maintaining immune homeostasis. Its immunosuppressive effects have been harnessed therapeutically via administration of low cytokine doses. Low-dose IL-2 has shown promise in the treatment of various autoimmune and inflammatory diseases; however, the clinical use of IL-2 is complicated by its toxicity, its pleiotropic effects on both immunostimulatory and immunosuppressive cell subsets, and its short serum half-life, which collectively limit the therapeutic window. As a result, there remains a considerable need for IL-2-based autoimmune disease therapies that can selectively target regulatory T cells with minimal off-target binding to immune effector cells in order to prevent cytokine-mediated toxicities and optimize therapeutic efficacy. In this review, we discuss exciting advances in IL-2 engineering that are empowering the development of novel therapies to treat autoimmune conditions. We describe the structural mechanisms of IL-2 signaling, explore current applications of IL-2-based compounds as immunoregulatory interventions, and detail the progress and challenges associated with clinical adoption of IL-2 therapies. In particular, we focus on protein engineering approaches that have been employed to optimize the regulatory T-cell bias of IL-2, including structure-guided or computational design of cytokine mutants, conjugation to polyethylene glycol, and the development of IL-2 fusion proteins. We also consider future research directions for enhancing the translational potential of engineered IL-2-based therapies. Overall, this review highlights the immense potential to leverage the immunoregulatory properties of IL-2 for targeted treatment of autoimmune and inflammatory diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 11738804
- Volume :
- 38
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- BioDrugs
- Publication Type :
- Academic Journal
- Accession number :
- 175846952
- Full Text :
- https://doi.org/10.1007/s40259-023-00635-0