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decoy-resistant IL-18 mRNA
- Development stage
- Preclinical
- Lead developer
- Universidad de Navarra
- Modality
- mRNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Gene Therapies
- Administration
- Intratumoral
01
Overview
DR-18 mRNA is an mRNA-based gene therapy encoding a modified version of interleukin-18 (IL-18) known as decoy-resistant IL-18 (DR-18). Standard IL-18 activity is often neutralized by the high-affinity endogenous decoy receptor IL-18 binding protein (IL-18BP), which is frequently upregulated in the tumor microenvironment. DR-18 is engineered to maintain its bioactivity and binding to the IL-18 receptor while being unable to bind to IL-18BP, thereby bypassing this immune inhibitory mechanism. In preclinical studies, intratumoral administration of DR-18 mRNA, particularly in combination with IL-12 mRNA, has demonstrated potent synergistic effects in inducing interferon-gamma (IFNγ) release and enhancing the activity of CD8+ T cells and cDC1 dendritic cells, leading to improved local and systemic antitumor immunity.
- Other names
- decoy-resistant interleukin-18 mRNAIL-18 decoy-resistant mRNAIL18 decoy-resistant mRNAIL 18 decoy-resistant mRNA
02
Targets
IL-18R (Interleukin-18 receptor complex)
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