Ernst Lab

University of Colorado Denver

PEDIATRICS

Aurora · United States

NIH-funded
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NIH R01 · 2024

Escape from CAR T surveillance through lineage plasticity

PROJECT SUMMARY Cancer cell genomic plasticity can enable resistance to cancer therapy for both solid tumors and hematologic malignancy. Escape from cytotoxic or molecularly targeted therapy through an inherent capacity to reprogram differentiation state or lineage has now been described following adoptive cell therapy or immune checkpoint blockade in adult epithelial tumors. Transfer of T cells genetically modified to express chimeric antigen receptors (CAR T cells) targeting the B cell surface antigen CD19 induces remission in 70-90% of patients with relapsed/refractory B cell acute lymphocytic leukemia (B-ALL) resulting in FDA-approval for this indication. However, a large fraction of…

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