IL-7Rα signaling potentiates the anti-tumor activity of NK92 cells

Background: Natural killer (NK) cells are promising candidates for cancer immunotherapy due to their safety and potent anti-tumor activity. However, their therapeutic efficacy is often limited by poor persistence and activity within the tumor microenvironment (TME) caused by a lack of essential cytokines. Methods: anti-tumor efficacy was assessed using a metastatic leukemia xenograft mouse model. Results: , NK92-IL-7R-IM cells demonstrated significantly potent anti-tumor activity and extended survival compared to control groups. Furthermore, the IL-7R-IM strategy successfully enhanced the function of CAR-NK cells targeting EphA2, EGFR, and CD5 antigens. Conclusions: The expression of IL-7R-IM confers cytokine independence and robust anti-tumor activity to NK and CAR-NK cells. This strategy offers a practical solution to improve the persistence and efficacy of off-the-shelf NK cell therapeutics for clinical application.