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Mesothelin (MSLN) is highly expressed in ovarian cancer, making it a promising target for immunotherapy. Given this target profile, the authors developed a novel T\u2010cell receptor (TCR)\u2010like chimeric antigen receptor (CAR) T\u2010cell therapy targeting MSLN, designated KT127.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A first\u2010in\u2010human, dose\u2010escalation trial of KT127 was conducted following preclinical evaluation in vitro and in vivo. A combination of rapid titration and a standard \u201c3\u00a0+\u00a03\u201d dose\u2010escalation design was implemented. Eleven patients received KT127 at doses ranging from 1\u00a0\u00d7\u00a010\n                      <jats:sup>6<\/jats:sup>\n                      to 2\u00a0\u00d7\u00a010\n                      <jats:sup>7<\/jats:sup>\n                      cells\/kg following lymphodepletion. The primary objectives were to assess the safety and tolerability of KT127. Secondary objectives included overall survival, disease control rate (DCR), and progression\u2010free survival as efficacy measures. Quality of life (QOL) was assessed using the European Organisation for Research and Treatment of Cancer QLQ\u2010OV28 questionnaire.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No dose\u2010limiting toxicities, cytokine release syndrome, or immune effector cell\u2010associated neurotoxicity syndrome were observed. The DCR was 80% (95% confidence interval, 44.4%\u201397.5%). QOL assessments indicated improvement in abdominal\/gastrointestinal symptoms post\u2010treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.037), with no significant deterioration in other domains. Proteomic analysis identified differential expression of kallikrein\u2010related peptidases (KLK13, KLK14) and chemokine CXCL17 at baseline, potentially linked to treatment outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study highlights that KT127 has a manageable safety profile and shows preliminary biological activity in patients with advanced ovarian cancer, particularly those who have failed multiple lines of therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70279","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:46:11Z","timestamp":1769190371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["T\u2010cell receptor\u2013like chimeric antigen receptor T cells targeting mesothelin: A first\u2010in\u2010human dose\u2010escalation trial for platinum\u2010resistant advanced ovarian cancer"],"prefix":"10.1002","volume":"132","author":[{"given":"Yiyang","family":"Shan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Zhongda Hospital School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Zhongda Hospital School of Medicine Southeast University  Nanjing China"},{"name":"Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ji","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine  Nanjing China"},{"name":"Department of Clinical Science and Research Zhongda Hospital School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Zhongda Hospital School of Medicine Southeast University  Nanjing China"},{"name":"Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine  Nanjing China"},{"name":"Department of Clinical Science and Research Zhongda Hospital School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Zhongda Hospital School of Medicine Southeast University  Nanjing China"},{"name":"Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing CART Medical Technology Co., Ltd  Nanjing China"},{"name":"Department of Pathology The Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"},{"name":"Clinical Pathological Diagnosis &amp; Research Center Youjiang Medical University for Nationalities  Baise China"},{"name":"The Key Laboratory of Molecular Pathology (Hepatobiliary Diseases) of Guangxi  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing CART Medical Technology Co., Ltd  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3313-5062","authenticated-orcid":false,"given":"Yang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Zhongda Hospital School of Medicine Southeast University  Nanjing China"},{"name":"Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine  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