RESET: A TCR-coupled antigen receptor with superior targeting sensitivity and reversible drug-regulated anti-tumor activity.

ABSTRACT: Chimeric antigen receptor (CAR) T cells are effective cancer therapies, particularly in indications with high, stable, and tumor-specific antigen expression. Other settings may require improved targeting sensitivity, controllable targeting selectivity, and/or additional potency enhancements to achieve robust efficacy. Here, we describe a novel receptor architecture called RESET (rapamycin-enabled, switchable endogenous T cell receptor) that combines (1) cell surface antigen targeting, (2) small-molecule regulation, and (3) the signaling proficiency and inherent sensitivity of native T cell receptors. RESET-T cells outperformed both constitutive and drug-regulated CAR-T cells and show hallmarks of TCR activation that suggest improved fidelity to native T cell responses. Pharmacological cont

SUBMITTER: Leleux J 

PROVIDER: S-EPMC11997482 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature