A novel preclinical tool to unlock the potential of IL-18 in cancer immunotherapy: genO-hIL-18-hIL-18R mice

Background: Interleukin-18(IL-18) has emerged as a promising immunomodulatory cytokine in immuno-oncology due to its ability to enhance both innate and adaptive immune responses. It promotes IFN-γ production by T and NK cells, thereby amplifying anti-tumor immunity, especially when combined with checkpoint inhibitors or engineered pro-drugs to resist natural inhibition by IL-18BP. Recent studies suggest that IL-18-based therapies may overcome resistance mechanism in “cold” tumors, making them responsive to immunotherapies. Humanized mouse models expressing human IL-18R are essential to accurately assess efficacy and guide development of human-directed IL-18-based therapies. Therefore, we describe here a new IL-18/IL-18R double humanized mouse model to assess the efficacy of therapeutics targeting the IL-18/IL-18R axis.

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