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

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.