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First-in-Class CAR T Cell Therapy Selectively Eliminates Mutant Calreticulin-Driven Malignancies in a Fibrotic Niche

GSE295557 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2026/04/23 Platform GPL34284
Summary
Pathogenic mutations in calreticulin (mutCALR) are found in one third of patients with myeloproliferative neoplasms. All mutCALR variants yield the same protein neoepitope that forms an aberrant complex with the thrombopoietin receptor, driving oncogenic stem cell expansion, megakaryocyte hyperplasia and fibrosis. We developed a novel, first-in-class chimeric antigen receptor (CAR) T-cell therapy targeting mutCALR and evaluated efficacy in a bespoke human chimeroid model of the bone marrow. We used 10x single-cell RNA sequencing (scRNA-seq) to analyze cell composition, transcriptional differences, and cell-cell interactions.
Published in
CAR T cell therapy selectively depletes disease-driving mutant calreticulin cells in xenotransplants and human organoid models of myelofibrosis
Rampotas A, Wong ZC, Gannon I et al. · Science translational medicine 2026 · PMID 42384776 · doi:10.1126/scitranslmed.adz3553
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Also filed as BioProject PRJNA1255181 and SRA study SRP581160. Searching any of these in the dataset finder brings you back here.

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