Science Highlights
Published on July 30, 2025
Effects of IFN-γ on CD28-based CAR T cells in liquid and solid tumors
by Science
Bailey SR, Takei HN, Escobar G, et al. IFN-γ-Resistant CD28 CAR T Cells Demonstrate Increased Survival, Efficacy, and Durability in Multiple Murine Tumor Models. Science Translational Medicine. 2025; 17 (801) (doi: 10.1126/scitranslmed.adp8166).
Researchers present evidence, collected from several tumor models in mice, demonstrating the benefits of inhibition of interferon γ (IFN-γ) signaling in the setting of both hematologic and solid tumors. For example, targeting IFN-γ or IFN-γ receptor interrupts apoptosis of chimeric antigen receptor (CAR) T cells with a CD28 intracellular signaling domain. Other models show that knockout of IFN-γ receptor boosts the persistence of T cells without sacrificing efficacy in hematologic malignancies and equips them with better tumor control, longer survival, and improved cell memory in solid tumors. Additionally, based on RNA sequencing of tumor-infiltrating IFN-γ receptor CAR T cells from tumor-bearing mice, inhibition of IFN-γ signaling expands cell death in tumor cells. Collectively, the findings reflect the complex role that interferon-gamma plays in cancer.
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