Novel preclinical mouse model to investigate IL-18-targeting therapies

Background

Interleukin-18 (IL-18) is an immunomodulatory cytokine with growing relevance in immuno-oncology due to its capacity to potentiate both innate and adaptive immune responses. It promotes IFN-γ production in T and natural killer (NK) cells, thereby amplifying anti-tumor immunity. Recent evidence suggests that IL-18–based therapies may help overcome resistance in immunologically “cold” tumors1 and could be combined with checkpoint inhibitors, such as PD-1 blocking antibodies to overcome IL-18BP natural inhibition. Robust preclinical evaluation of human targeted IL-18 therapeutics requires models that faithfully recapitulate the human IL-18/IL-18R axis and enable assessment of combination strategies with PD-1–targeting therapies. Therefore, we generated and characterized humanized mouse models expressing human IL-18, human IL-18 receptor, and human PD-1 (genO-hIL-18/hIL-18R and genO-hIL-18/hIL-18R/hPD-1).

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