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Natural killer (NK) cell lines are promising platforms for CAR constructs due to their inherent tumor\u2010killing ability, safety profile, and feasibility for standardized, off\u2010the\u2010shelf therapeutic use. Herein, four human NK cell lines (YT, KHYG1, NKL, and NK92) were retrovirally transduced with an anti\u2010Hsp70 CAR targeting membrane\u2010bound heat shock protein 70 (mHsp70), a tumor\u2010specific antigen with broad expression on many solid tumors, but not normal cells. Computational modeling suggested a strong binding between the CAR and the extracellular domain of mHsp70. Although all NK cell lines exhibited successful CAR integration and surface expression, only NKL and NK92 cells maintained stable CAR expression and long\u2010term viability. The anti\u2010Hsp70 CAR NKL and NK92 cells demonstrated enhanced expression of activation markers and secretion of cytotoxic effector molecules, and robust target\u2010specific killing of mHsp70\u2010positive cancer cells, while sparing mHsp70\u2010negative targets. Our findings validate the therapeutic potential of anti\u2010Hsp70 CAR NK cells and the suitability of NKL and NK92 cells for advancing off\u2010the\u2010shelf CAR NK cell therapies, thereby offering a promising strategy for targeting a broad range of solid tumors expressing mHsp70.<\/jats:p>","DOI":"10.1002\/mco2.70753","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:46:53Z","timestamp":1778478413000},"source":"Crossref","is-referenced-by-count":2,"title":["Development of CAR NK Cell Lines Selectively Targeting Cancer Cells Expressing Membrane Hsp70"],"prefix":"10.1002","volume":"7","author":[{"given":"Khouloud","family":"Hachani","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery TUM School of Medicine and Health Technical University of Munich  Munich 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