GVHD can be reversed using an IL-6^−/− donor in a delayed DLI model. (A) Survival curve of WT B6 or IL-6^−/− leukemia-bearing mice treated with syngeneic CAR (B6 or IL-6^−/−) following nonlethal radiation on day −1, without a BMT. (B) Survival curve of leukemia-bearing CAR T recipients with either B6 → C3h.sw setup (red) or using IL-6^−/− mice as marrow and T cell donors (blue), with syngeneic B6 → B6 controls (gray). (C) Survival curve for leukemia-bearing CAR T recipients of syngeneic (gray), allogeneic B6 → C3h.sw treated with anti–IL-6 receptor antibody (blue), or isotype control IgG (red). (D) Delayed CAR-DLI model: at 12 days post-TCD–BMT mice were challenged with leukemia (10⁶ cells/mouse), followed by cyclophosphamide 4 mg/mouse on day 16 and 10⁶ CAR/mock T cells on day 17. WT B6 or IL-6^−/− were used as marrow donors and all T cells were B6-CD45.1 derived, as indicated in graphs. (E) Survival curve with this delayed CAR model (P = .012; B6 vs IL-6^−/− → C3h.sw CAR). (F) Clinical GVHD score in delayed CAR model. All in vivo experiments conducted with 5 mice per group and plots shown are representative of at least 2 separate experiments.