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Chimeric antigen receptor (CAR) T\u2010cell therapy targeting fibroblast activation protein (FAP), a marker of CAFs, has gained attention and is being evaluated in both preclinical and clinical studies. Cord blood (CB)\u2010derived CAR natural killer (NK) cell therapy has shown efficacy in hematologic malignancies. In this study, we generated FAP\u2010targeting CAR NK cells (FAP\u2010CAR NK cells). CD3\u2010depleted CB mononuclear cells were stimulated with irradiated K562 cells expressing 4\u20101BB ligand (tumor necrosis factor ligand superfamily member 9) and membrane\u2010bound interleukin\u201015 and interleukin\u201021 to expand NK cells, into which FAP\u2010CAR was introduced. FAP\u2010CAR NK cells produced cytokines and exerted cytotoxic activity when co\u2010cultured with FAP\u2010transduced HT1080 cells and CAFs isolated from human lung cancer tissue. In a xenograft model established by intrathoracic co\u2010injection of A549 lung cancer cells and luciferase\u2010expressing CAFs, injection of FAP\u2010CAR NK cells, but not control CD19\u2010CAR NK cells, resulted in their robust expansion and persistence in\u00a0vivo for 5\u2009weeks. However, CAFs were not eliminated by FAP\u2010CAR NK cells, although CAR NK cells were clearly detected in the tumors. The levels of cytotoxicity\u2010associated molecules (such as granzymes) were higher in FAP\u2010CAR NK cells persisting in the spleens of mice compared with those in pre\u2010infusion FAP\u2010CAR NK cells. These results indicate that FAP\u2010CAR NK cells have the potential to respond specifically to the target antigen and expand robustly in\u00a0vivo, although further optimization is required to maintain cytotoxic function for a prolonged duration in\u00a0vivo.<\/jats:p>","DOI":"10.1111\/cas.70539","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:55:55Z","timestamp":1789952155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cord Blood\u2010Derived Fibroblast Activation Protein\u2010Targeted Chimeric Antigen Receptor Natural Killer Cells Persist in Vivo"],"prefix":"10.1111","author":[{"given":"Takashi","family":"Hiroshima","sequence":"first","affiliation":[{"name":"Department of General Thoracic Surgery The University of Osaka Graduate School of Medicine  Suita 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