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Due to the high expression of mesothelin in this cancer, anti\u2010PD\u20101 nanobody\u2010armored mesothelin\u2010targeting CAR\u2010T (NAC\u2010T) cells are developed. Based on the enhanced anti\u2010tumor activity observed in preclinical in vitro and in vivo studies, a first\u2010in\u2010human clinical trial is initiated. Eleven patients with malignant mesothelioma who have progressed after standard therapies receive intravenous infusions of 5\u201320 \u00d7 10\n                    <jats:sup>6<\/jats:sup>\n                    per kg NAC\u2010T cells following lymphodepletion. The treatment is well tolerated, with no dose\u2010limiting toxicity observed. The overall response rate is 63.6%, including one complete response, and the disease control rate is 100%. The median progression\u2010free survival is 5.0 months, and the median overall survival is 25.6 months. Moreover, T cell receptor and single\u2010cell sequencing analyses in patients with varying responses revealed specific clonal expansion of T cell subtypes and enhanced reactivity to tumor\u2010associated antigens. These findings suggest that NAC\u2010T cell therapy represents a promising therapeutic strategy for patients with malignant mesothelioma.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508754","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:14:25Z","timestamp":1761311665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti\u2010PD\u20101 Nanobody\u2010Armored MSLN CAR\u2010T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies"],"prefix":"10.1002","volume":"13","author":[{"given":"Yan","family":"Sun","sequence":"first","affiliation":[{"name":"School of Medicine Shanghai Mengchao Cancer Hospital Shanghai University  Shanghai 200444 China"},{"name":"Shanghai Cell Therapy Group Co. 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