Figure 6.

Allogeneic FKBP1A^KO 19CAR-T cells induce B cell aplasia in tacrolimus-treated HIS mice

(A) Four independent cohorts (6–9) of huNCG HIS mice were evenly distributed into groups: group 1 (n = 16) received allogeneic HLA-deficient (B2M^KOCIITA^KO) UTD T cells and VEH treatment, group 2 (n = 16) received allogeneic HLA⁺ CD19-specific CAR-T cells (19CAR) and VEH treatment, group 3 (n = 15) received allogeneic HLA⁺FKBP1A^KO 19CAR-T cells and TAC treatment, and group 4 (n = 16) received allogeneic HLA-deficient 19CAR-T cells and VEH treatment. All T cells were base edited to disrupt TCR expression. (B and C) Concentration (B) and FACS plots indicate frequency (C) of peripheral CD19⁺ B cells 6 days post-T cell infusion from mice in groups 1–4. (D and E) Total CD19⁺ B cells from individual mouse splenic (D) and bone marrow (E) tissue 10 days post-T cell infusion in groups 1–4. (F) Geometric median fluorescent intensity (MFI) of CD19 expression on peripheral CD22⁺ B cells 6 days post-T cell infusion from mice in groups 1–4. (G) Concentration of peripheral CD22⁺CD19^dim B cells 6 days post-T cell infusion from mice in groups 1–4. (H) FACS plots indicate frequency of EGFR⁺ 19CAR-T cells from mice in groups 2–4, 10 days post-T cell infusion. (I and J) Peripheral concentration of 19CAR-T cells (I) and total splenic 19CAR-T cells (J) from mice in groups 2–4, 10 days post-T cell infusion. For all data, bars reflect mean, error bars show ±SEM, and symbols indicate biologically independent animals. Statistical significance was calculated by Wilcoxon rank-sum test (B, D, and E) and Kruskall-Wallace test with Dunn’s test for multiple comparisons (F, G, I, and J).