Figure 7 from Activation of Cell-Intrinsic Signaling in CAR-T Cells via a Chimeric IL7R Domain

Single-chain proximal IL7Rα CAR-T cells have decreased in vivo antileukemia activity. A, Schematic of the xenograft model. On day 0, NSG mice were injected via tail vein with 1 × 10⁶ CD123⁺ MV-4-11.ffLuc cells. In treatment groups, 2 × 10⁶ CAR⁺ T cells were administered via tail vein on day 7. Cohorts: unmodified (NT, n = 2), CD28.ζ + sIL7 (n = 6), CD28.IL7R.ζ (n = 6), and IL7R.CD28.ζ (n = 5) T cells. Untreated mice (n = 3) served as controls. B, Representative mouse pictures of leukemia proliferation monitored with BLI. C, Radiance. Dotted lines, individual mice; solid line, median of each cohort. D, Kaplan–Meier survival analysis; comprehensive curve comparison; P < 0.0001; NT vs. CD28.ζ_sIL7, vs. CD28.IL7R.ζ, and vs. IL7R.CD28.ζ: all **, P < 0.01 individual comparisons. CD28.IL7R.ζ vs. IL7R.CD28.ζ: *, P < 0.01. E, AML and (F). T-cell counts detected in peripheral blood of mice and measured by flow cytometry. No significant differences found between groups. NSG, NOD/SCIDγ; NT, nontransduced.