Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality

Abstract

Engineered T cells work as living therapeutics, but are prone to hyperreactivity and exhaustion. Here the authors improve CAR T cell antitumor responses by simultaneously targeting a CAR to TCR locus and IL-12 to PD1 locus, placing the transgenes under a naturally regulated transcriptional network while disrupting unwanted signals.