Sustained and specific multiplexed immune checkpoint modulation in CAR T cells induced by targeted epigenome editing.

ABSTRACT: Engineered T cells equipped with a chimeric antigen receptor (CAR) have shown tremendous clinical success, but tumor-mediated stimulation of T cell inhibitory receptors leads to exhaustion, hampering durable remission in patients. Mitigation of this effect via checkpoint inhibition or genome editing to knockout the genes encoding for these receptors has shown promise. Yet, the side effects of these procedures require better alternatives. Targeted epigenome editing offers a potent strategy to alter gene expression without DNA modifications. Its hit-and-run mechanism enables durable, multiplexed modulation of gene expression with greater safety. Here, we describe multiplexed epigenome editing inactivation of two critical-exhaustion-related genes, PDCD1 and LAG3, both in primary

SUBMITTER: Roman Azcona MS 

PROVIDER: S-EPMC12275148 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature