ShRNA-based PD-1 suppression preserves memory phenotype and function of CD19-targeted CAR-T cell.

ABSTRACT:

Background

Chimeric antigen receptor T cell (CAR-T) therapy targeting cluster of differentiation 19 (CD19) has shown promise in treating B-cell acute lymphoblastic leukemia (B-ALL), but the long-term efficacy of CD19-targeted CAR-T therapy remains limited. Programmed cell death protein 1 (PD-1), an inhibitory receptor on activated T cells, engages programmed death ligand 1 (PD-L1) in the tumor microenvironment, suppressing CAR-T cell function by impairing key signaling pathways. To address this limitation, we investigated the effect of short hairpin RNA (shRNA)-mediated PD-1 knockdown on alleviating CAR-T cell exhaustion, preserving memory phenotype, and enhancing the long-term efficacy of CD19-targeted CAR-T cells.

Methods

To overcome this limitation, we employed shRNA to a

SUBMITTER: Zhao J 

PROVIDER: S-EPMC12605615 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature