IL-2/anti-IL-2 mAb imunokomplexy a polymerně modifikovaný IL-2 jako účinné imunomodulátory

Weberová, Petra

Interleukin-2 (IL-2) is recognized as a crucial cytokine for the proliferation, survival, and expression of effector functions in activated T and NK cells. However, IL-2 is involved not only in promoting effector T and NK cell functions but also in maintaining immune homeostasis, as it is an essential cytokine for the survival, proliferation, and suppressive activity of T regulatory (Treg) cells. This dual functionality makes IL-2 a potential immunotherapeutic drug for both cancer and autoimmune disease treatment, exploiting the differential expression of IL-2 receptor (IL-2R) subunits between Treg and effector cells. However, the therapeutic use of IL-2 is limited by its short half-life and significant dose-dependent adverse effects. To address these challenges, recent innovations such as IL-2/anti-IL-2 monoclonal antibody (mAb) immunocomplexes (IL-2co), IL-2 muteins with a modified affinity for some IL-2R subunit(s), and polymer-modified IL-2 have been developed. These advancements aim to refine the therapeutic profile of IL-2, enhancing its selectivity, efficacy, and safety. In this thesis, I present several original studies in which we explored both current and new approaches to modify IL-2. Through molecular engineering and protein chemistry, we developed various novel IL-2 formulations: a...

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