Effects of CRISPR-Cas9-mediated <i>FOXP3</i> knockout on CAR T cell potency.

ABSTRACT: Persistent antigen stimulation and inflammatory environments drive exhaustion, senescence, and activation-induced cell death, impairing both endogenous and therapeutic T cells. Understanding the mechanisms underlying T cell dysfunction is critical for improving immunotherapies. While the transcription factor forkhead box protein P3 (FOXP3) is primarily known for its role in regulatory T cell development and maintenance, recent studies suggest it may also influence effector T cell function. However, its impact on therapeutic T cells, including CAR T cells, remains poorly defined. Here, we used non-viral CRISPR-Cas9 editing to knockout FOXP3 in CD19-directed CAR T cell products (TCPs) generated via lentiviral transduction. FOXP3 expression was upregulated at both the protein and RNA l

SUBMITTER: Peter L 

PROVIDER: S-EPMC12433514 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature