{
  "abstract": "First clinical trials demonstrated the safety of adoptive cell transfer with allogeneic natural killer (NK) cell products from healthy donors, making them an attractive candidate for ‘off-the-shelf’ chimeric antigen receptor (CAR)-immune cell therapy. However, reduced persistence and inactivation of NK cells by immunosuppressive cues likely limit the performance of CAR-redirected NK cells. Wang and colleagues demonstrate that multiplex CRISPR base editing allows optimization of the intrinsic functionality of CAR-NK cells improving their therapeutic potential. In contrast to conventional CRISPR-Cas nucleases, base editing avoided most double-stranded DNA breaks while enabling highly efficient editing at up to six sites simultaneously. The study further demonstrates the feasibility of a non-viral approach to integrate CAR transgene and multiplex base editing of several immune checkpoints in NK cells using a single electroporation. CAR-NK cells harboring up to three base edits demonstrate improved potency over unedited counterparts in vitro. Xenograft mouse models confirmed increased potency, but also indicated signs of organ toxicity - a phenomenon that will require future studies prior to clinical translation. The study demonstrates that CRISPR base editing is a powerful tool to unleash the full cytotoxic potential of NK cells, but it also warrants the question: How many internal breaks can be removed without hurting CAR-NK cell therapy’s impeccable safety record?",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatrics, Experimental Immunology and Celltherapy, Goethe University Frankfurt, Frankfurt am Main, Germany",
        "Institute for Transfusion Medicine and Immunohematology, German Red Cross Hesse, Frankfurt am Main, HE, Germany",
        "Berlin Center for Advanced Therapies, Charité - Universitätsmedizin Berlin, Berlin, BE, Germany"
      ],
      "name": "Tobias Bexte"
    },
    {
      "affiliations": [
        "Berlin Center for Advanced Therapies, Charité - Universitätsmedizin Berlin, Berlin, BE, Germany",
        "Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA",
        "Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA",
        "Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité, Berlin, BE, Germany"
      ],
      "name": "Dimitrios L. Wagner"
    }
  ],
  "title": "Next-generation multiplex-edited CAR-NK cells: more edits, more power?",
  "uid": "f1b25268-7261-5e78-a66a-b7210db042b5"
}