IFNg Not Necessary for CAR-T Efficacy in Hematologic Malignancies

Bailey SR, Vatsa S, Larson RC, et al. Blockade or Deletion of IFNg Reduces Macrophage Activation Without Compromising CAR-T Function in Hematologic Malignancies. Blood Cancer Discovery. 2021; (doi: 10.1158/2643-3230.BCD-21-0181).

Researchers report that chimeric antigen receptor T cell (CAR-T) therapy effectively treats hematologic malignancies even in the absence of interferon-gamma (IFNg), which normally acts as a potency assay for CAR-T cells. Their study findings indicate this role is not essential for CAR-T therapy to do its job and that blocking IFNg actually has benefits. Inhibiting production through pharmacologic intervention or via genetic knockout mitigates cytokine release syndrome, a toxicity induced by activated CAR-T cells and innate immune cells. Blockade curbs immune checkpoint protein expression and also reduces macrophage activation more so than other approaches. Importantly, persistence is not lost and anti-tumor effect is maintained even during IFNg deletion.

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