Precise Control of Switchable Chimeric Antigen Receptor T Cells Allows Enhanced Safety and Less T Cell Exhaustion.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapies have achieved remarkable success in treating hematologic malignancies, yet their clinical utility remains limited by safety concerns, poor persistence, and T-cell exhaustion driven by continuous receptor signaling. Although switchable CAR systems offer external control, most existing designs are irreversible, binary, or compromising CAR-T potency. Here, we introduce a chemically switchable CAR platform that enables graded, reversible regulation of CAR-T activity while retaining full therapeutic capacity. Using engineered CAR-T cells, we evaluate drug-controlled activation, cytotoxicity, and cytokine release against CD19⁺ tumor cells and screened clinically approved NS3/4A inhibitors to identify optimal small-molecule controllers. Compared wi

SUBMITTER: Zhang ZA 

PROVIDER: S-EPMC12715549 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature