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<p>CAR-T cell therapy has been transformative in treating certain blood malignancies and is also being adopted for treating other malignancies, including solid tumors. Despite its undeniable successes, CAR-T cell therapy is frequently associated with severe and potentially life-threatening side effects and toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), graft-versus-host disease (GvHD) in allogeneic settings, secondary CAR-T-derived malignancies, and long-term immunosuppression-induced risk of infections. Recent advances in integrating gene-editing technology and nanomedicine into CAR-T cell therapy have opened new avenues to enhance the safety profile of CAR-T cell therapy and broaden its clinical applications. Gene-editing tools enable targeted modulation of the CAR-T cells' genome, thereby improving their safety profile by preventing related side effects. In parallel, nanomedicine can be used at various stages, including manufacturing and post-treatment, to prevent their occurrence or manage them. This review highlights the current preclinical and clinical landscape, explores the emerging combinatorial strategies, and discusses future directions to achieve a safe and more controllable CAR-T cell therapy.</p>

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Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology

  • 期刊论文

  • 发表日期：

    2026年1月4日

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  • Jinxin Dong,
  • Denis Andreevich Nikolenko,
  • Shuxrat Boymuradov,
  • Lilya Garifulina,
  • Elnaz Khodabandehloo

摘要

CAR-T cell therapy has been transformative in treating certain blood malignancies and is also being adopted for treating other malignancies, including solid tumors. Despite its undeniable successes, CAR-T cell therapy is frequently associated with severe and potentially life-threatening side effects and toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), graft-versus-host disease (GvHD) in allogeneic settings, secondary CAR-T-derived malignancies, and long-term immunosuppression-induced risk of infections. Recent advances in integrating gene-editing technology and nanomedicine into CAR-T cell therapy have opened new avenues to enhance the safety profile of CAR-T cell therapy and broaden its clinical applications. Gene-editing tools enable targeted modulation of the CAR-T cells' genome, thereby improving their safety profile by preventing related side effects. In parallel, nanomedicine can be used at various stages, including manufacturing and post-treatment, to prevent their occurrence or manage them. This review highlights the current preclinical and clinical landscape, explores the emerging combinatorial strategies, and discusses future directions to achieve a safe and more controllable CAR-T cell therapy.