CD19-BBz CAR-T cells with Notch1 PEST domain editing

CD19-BBz CAR-T cells with Notch1 PEST domain editing are an experimental cell therapy designed to treat B-cell malignancies. These T-cells are engineered to express a chimeric antigen receptor (CAR) targeting CD19 with a 4-1BB (BBz) costimulatory domain. Additionally, CRISPR-Cas9 technology is used to truncate the PEST domain of the endogenous Notch1 protein. The PEST domain normally regulates the degradation of the Notch1 intracellular domain (N1ICD); its truncation mimics mutations found in T-cell acute lymphoblastic leukemia (T-ALL), leading to prolonged N1ICD stability upon T-cell activation. This modification enhances CAR T-cell proliferation, survival, cytokine secretion, and metabolic fitness, potentially overcoming T-cell intrinsic deficits that lead to relapse in patients treated with standard CAR-T therapies.

Other names

Notch1 PEST-edited CD19 CAR-T cellsNotch-1 PEST-edited CD19 CAR-T cellsNotch 1 PEST-edited CD19 CAR-T cellsPEST-truncated CD19-BBz CAR-T cells