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Updated: Jan 11, 2026

Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells
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JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian

Charles Joseph Kuhlmann1, Chloe E Jepson1, Madison T Blucas1

  • 1Department of Microbiology, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.

Journal for Immunotherapy of Cancer
|November 18, 2025
PubMed
Abstract

Insights

Targeting c-Jun N-terminal kinases (JNK) enhances chimeric antigen receptor T (CAR-T) cell therapy against solid tumors. This strategy boosts CAR-T cell antitumor activity by modulating nuclear factor of activated T cells (NFAT) signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Therapy

Background:

  • Chimeric antigen receptor T (CAR-T) cell therapy shows promise for cancer treatment.
  • Improving CAR-T cell efficacy in solid tumors is a critical clinical need.
  • Nuclear factor of activated T cells (NFAT) signaling is crucial for T cell function.

Purpose of the Study:

  • To investigate the role of c-Jun N-terminal kinases (JNK) in regulating CAR-T cell activity.
  • To determine if targeting JNK can enhance CAR-T cell-mediated antitumor responses.
  • To explore the impact of JNK modulation on NFAT signaling in CAR-T cells.

Main Methods:

  • Developed lentivirally encoded short-hairpin RNA for stable JNK knockdown in CAR-T cells.
  • Generated CAR-T cells targeting human epidermal growth factor receptor 2 from human peripheral blood.
  • Assessed CAR-T cell functionality in vitro and in human ovarian cancer xenograft models.

Main Results:

  • JNK knockdown suppressed antigen-induced stimulation and helper T cell cytokine production.
  • JNK-deficient CAR-T cells exhibited enhanced antitumor cytotoxicity in vitro and in vivo.
  • Mechanistically, JNK knockdown altered NFAT signaling, promoting NFATc1-dependent transcription and granzyme B expression.

Conclusions:

  • JNK signaling significantly regulates CAR-T cell cytotoxicity.
  • Targeting JNK represents a viable strategy to enhance CAR-T cell effectiveness in cancer therapy.
  • Modulating JNK offers a direct approach to improve CAR-T cell performance against solid tumors.
Keywords:
Chimeric antigen receptor - CARImmunotherapyOvarian CancerT cell

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