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**TSLPR CAR T-cells** are autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the thymic stromal lymphopoietin receptor (TSLPR), overexpressed in 5-15% of B-cell acute lymphoblastic leukemia (B-ALL) cases due to CRLF2 rearrangements or other alterations, particularly in high-risk Ph-like ALL and Down syndrome-associated ALL. The CAR typically uses a 3G11-derived scFv for TSLPR binding, with a short spacer design (CD8 transmembrane domain), 4-1BB costimulatory domain, and CD3ζ signaling domain for optimal persistence and efficacy; long spacer versions (with CH2CH3) show reduced activity. Developed by researchers at MD Anderson Cancer Center and advanced toward IND by UPenn/CHOP, these cells demonstrate potent in vitro cytotoxicity, eradication of TSLPR-high B-ALL in xenograft and PDX models even at high tumor burden, and limited expression on normal tissues (e.g., myeloid dendritic cells), minimizing toxicity.[1][2][3][4][5][8]
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