JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian cancer models.

ABSTRACT:

Background

Boosting the performance of chimeric antigen receptor T (CAR-T) cell therapy in solid tumors may provide a substantial advantage for patients with cancer. Recognizing the vital role of the nuclear factor of activated T cells (NFAT) in T cell function, we hypothesized the strategic regulation of NFAT activity by targeting c-Jun N-terminal kinases (JNK) can bolster the tumor-eradicating potential of CAR-T cells.

Methods

We developed a lentivirally encoded short-hairpin RNA for stable knockdown of JNK in CAR-T cells. CAR-T cells targeting human epidermal growth factor receptor 2 were produced from human peripheral blood. Functionality was tested in vitro and in two xenograft models of human ovarian cancer.

Results

JNK knockdown in CAR-T cells suppressed antige

SUBMITTER: Kuhlmann CJ 

PROVIDER: S-EPMC12636948 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature