Leukemia eradication in human CRLF2-rearranged Ph-like ALL patient-derived xenograft models by short TSLPR CAR T cells. (A) Flow cytometric surface expression of CD19 and TSLPR in human ALL cells from TSLPRhi PDX models JH352, NH362, and JH331. Shaded histograms denoted by dotted lines represent unstained controls. (B) Complete eradication of leukemia in a TSLPRhi luciferase–expressing PDX model (JH331) by short TSLPR CAR T cells. ACT, adoptive cell transfer. (C-D) Analysis of human CD45⁺ CD19⁺ ALL cells in peripheral blood (C) and bone marrow (D) of TSLPRhi PDX models JH352 and NH362 injected with 1 × 10⁶ ALL cells per mouse, then treated 22 days later with 15 × 10⁶ short TSLPR CAR T cells. (E-G) Tissue analyses of an aggressive relapsed TSLPRhi ALL PDX model (ALL4364) treated with TSLPR CAR T cells. One million ALL cells per mouse were injected IV on day 1, then animals were treated with 1.2 million of TSLPR CAR⁺ T cells IV on day 14. (E) Spleens from short TSLPR CAR-treated and untreated mice on days 35 and 42 after leukemia injection (2 and 3 weeks after CAR injection). (F) Representative dot plot of bone marrow, spleen, and peripheral blood on day 35 after leukemia injection. (G) Scatter plots of organ and blood leukemia infiltration at day 35 after TSLPRhi ALL injection comparing short TSLPR CAR treated and untreated mice. (H) Separate experiment showing survival analysis demonstrating prolonged survival of TSLPR CAR T cell–treated ALL4364 PDX animals (n = 5/group). ACT, adoptive cell therapy. (I) Expression of TSLPR on human CD45⁺/CD19⁺ leukemia cells in the bone marrow of a mouse with relapse after short TSLPR CAR treatment.