PEBL-CAR T-cell activity against ETP-ALL in a patient-derived xenograft (PDX) model. (A) Primary ETP-ALL cells, previously propagated in NOD-SCID-IL2RGnull mice, were infused IV in 10 NOD-SCID-IL2RGnull mice at 2 × 10⁶ cells per mouse. Five mice (Control) were left untreated. The remaining 5 mice received a single IV infusion of PEBL-CAR T cells (2 × 10⁷ in PEBL-CAR#1 mouse, 2 × 10⁶ in the remaining 4 mice) at the indicated time point (blue arrow), as well as 20 000 IU IL-2 IP every 2 days; IL-2 was also administered to 2 of the 5 control mice. Red symbols (left y-axes) indicate the number of ETP-ALL cells per milliliter counted in peripheral blood. Blue symbols (right y-axes) show the numbers of PEBL-CAR T cells. The mice were euthanized when the percentage of ETP-ALL cells among blood mononucleated cells reached ≥80%. (B) The percentage of ETP-ALL (denominator, total human plus mouse CD45⁺ cells) in various organs of the 5 untreated mice. (C) Blood smears of treated (PEBL-CAR#1) and untreated ETP-ALL 7 days after infusion of T cells; smudge cells were prominent in blood after infusion of PEBL-CAR T cells. Original magnification ×40, Wright stain. (D) Flow cytometric dot plots show the presence of CD7⁺ CD3^– ETP-ALL cells in the tissues of an untreated control mouse with ETP-ALL and of CD7^– CD3⁺ PEBL-CAR T cells in the PEBL-CAR#1 mouse treated with PEBL-CAR T cells. No ETP-ALL (<0.01%) was detected in the treated mouse. The events shown were normalized to the events acquired for the corresponding plots shown in the control mouse. (E) Spleens of treated (PEBL-CAR#1) and untreated mice. BM, bone marrow.