hyper-IL-15

Hyper-IL-15 is a **fusion protein** composed of interleukin-15 (IL-15) complexed with the sushi domain of the IL-15 receptor alpha chain (IL-15Rα) and a human IgG1-Fc domain. This construct mimics the natural **trans-presentation mechanism** of IL-15, where IL-15 is presented in complex with IL-15Rα to activate immune cells expressing IL-2Rβ/γc receptors. The fusion protein design significantly enhances the **biological activity and pharmacokinetic profile** of IL-15 compared to IL-15 alone[1][2][6]. Hyper-IL-15 functions as an **IL-15 superagonist** that robustly expands and activates natural killer (NK) cells and CD8+ T cells, particularly tumor-specific CD8+ T cells[2]. Upon administration, it binds to the IL-2/IL-15 receptor beta-common gamma chain (IL-2Rβ-γc) on NK cells and T lymphocytes, leading to enhanced proliferation, activation, and cytotoxic activity of these immune cells[4]. The molecule triggers production of pro-inflammatory cytokines including IL-12 and interferon-gamma (IFN-γ), while reducing expression of co-inhibitory molecules on dendritic cells[2]. In preclinical studies using hydrodynamics-based gene delivery in mice, hyper-IL-15 demonstrated **remarkable therapeutic effects** against both well-established liver metastatic tumors and DEN-induced autochthonous hepatocellular carcinoma (HCC)[2]. The anti-tumor effects were primarily mediated by CD8+ T cells rather than NK cells, with preferential expansion of tumor-specific CD8+ T cells and enhancement of their interferon-γ synthesis and cytotoxic functions[2]. The treatment achieved up to 100-fold reduction in total tumor volume in autochthonous HCC models[2].

Other names

IL-15/IL-15RαSu-FcIL-15/sIL-15RαhetIL-15hetIL15hetIL 15