Figure 5.

FKBP1A^KO 19CAR-T cells retain in vivo anti-tumor function in the presence of tacrolimus and rapamycin

(A) Schematic of drug treatment in xenograft tumor-bearing mouse model for (B)–(E). JeKo-1.Luc cells (5 × 10⁵) were transplanted into recipient NSG mice (n = 72), then 7 days later mice initiated vehicle (VEH) (n = 24), rapamycin (RPM) (n = 24), or tacrolimus (TAC) (n = 24) treatment daily for 2 weeks. One day later, mice from each treatment group were infused with 1 × 10⁶ untransduced (UTD) T cells (n = 8 per group), unmodified CD19-specific CAR-T cells (19CAR) (n = 8 per group), or FKBP1A^KO 19CAR-T cells (n = 8 per group). (B) Representative longitudinal bioluminescent flux imaging of JeKo-1.Luc-bearing NSG mice treated with TAC and UTD, 19CAR, or FKBP1A^KO 19CAR-T cells. (C) Longitudinal tumor burden (flux p/s) of T cell-treated mice that received VEH or TAC treatment. (D) Cumulative tumor burden of T cell-infused mice during the VEH or TAC treatment interval. (E) Longitudinal tumor burden of T cell-infused mice that received VEH or RPM treatment. (F and G) NSG mice were implanted with 5 × 10⁵ JeKo-1.FKBP1A^KO.Luc cells and 6 days later initiated VEH (n = 30) or RPM (n = 30) treatment daily for 2 weeks. One day after, mice from each treatment group were infused with either 1 × 10⁶ UTD T cells (n = 10 per group), unmodified 19CAR-T cells (n = 10 per group), or FKBP1A^KO 19CAR-T cells (n = 10 per group). (F) Longitudinal tumor burden of T cell-infused mice that received VEH or RPM treatment. (G) Cumulative tumor burden of T cell-infused mice during the VEH or RPM treatment interval. (C, E, and F) Vertical dotted line indicates T cell infusion. For all data, symbols and bars reflect means and error bars show ±SEM, except (D) and (G), where symbols represent individual mice. Sample sizes represent biologically independent animals. Statistical significance was calculated by Kruskall-Wallace test with Dunn’s test for multiple comparisons (D and G). AUC, area under the curve.