IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell malignancies

IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell malignancies

Blog Article

Abstract Antigen escape relapse is a major challenge in targeted immunotherapies, including CD19- and CD22-directed chimeric antigen receptor (CAR) T-cell for B-cell acute lymphoblastic Tops leukemia (B-ALL).To identify tumor-intrinsic factors driving antigen loss, we perform single-cell analyses on 61 B-ALL patient samples treated with CAR T cells.Here we show that low levels of IKAROS in pro-B-like B-ALL cells before CAR T treatment correlate with antigen escape.

IKAROSlow B-ALL cells undergo epigenetic and transcriptional changes that diminish B-cell identity, making Rattle Blanket them resemble progenitor cells.This shift leads to reduced CD19 and CD22 surface expression.We demonstrate that CD19 and CD22 expression is IKAROS dose-dependent and reversible.

Furthermore, IKAROSlow cells exhibit higher resistance to CD19- and CD22-targeted therapies.These findings establish a role for IKAROS as a regulator of antigens targeted by widely used immunotherapies and in the risk of antigen escape relapse, identifying it as a potential prognostic target.