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Targeting PTPN2 enhances human CAR T cell efficacy and the development of long-term memory [RNA-seq]

GSE309442 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2025/10/04 Platform GPL18573
Summary
CAR T cells have been ineffective against solid tumors, where the hostile tumor microenvironment limits CAR T cell function and persistence. Here we have used CRISPR/Cas9 gene-editing, or a small molecule inhibitor to target protein tyrosine phosphatase N2 (PTPN2) in human CAR T cells specific for the Lewis Y (LeY) neo-antigen. Targeting PTPN2 increased CAR and cytokine signaling and enhanced the activation and cytotoxicity of anti-LeY CAR T cells. The deletion or the systemic inhibition of PTPN2 in human CAR T cells repressed the growth of human tumor xenografts or patient-derived xenografts in mice and prolonged survival. PTPN2 deletion or inhibition promoted the generation and intratumoral accumulation of stem cell memory CD8+ CAR T cells that are associated with persistent CAR T cell-mediated tumor repression and improved clinical outcomes in patients. These findings support the use of gene-editing or small molecule inhibitors for targeting PTPN2 in human CAR T cells to combat solid tumors.
Published in
Targeting PTPN2 enhances human CAR T cell efficacy and the development of long-term memory in mouse xenograft models
Du X, Goh PK, Ma C et al. · Science translational medicine 2025 · PMID 41160667 · doi:10.1126/scitranslmed.adk0627
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Also filed as BioProject PRJNA1336086. Searching any of these in the dataset finder brings you back here.

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