T-cell receptor—like chimeric antigen receptor T cells targeting mesothelin: A first-in-human dose-escalation trial for platinum-resistant advanced ovarian cancer

Sep 22, 2026

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Background: Ovarian cancer is a major therapeutic challenge with late diagnosis, frequent recurrence, and limited options. Mesothelin (MSLN) is highly expressed in ovarian cancer, supporting immunotherapy targeting. The study developed KT127, a T-cell receptor—like chimeric antigen receptor (CAR) T-cell therapy directed to MSLN. Methods: A first-in-human, dose-escalation trial used rapid titration and a 3 + 3 design. Eleven patients received KT127 after lymphodepletion, with safety as the primary endpoint. Secondary endpoints included survival outcomes, disease control rate, progression-free survival, and QOL by QLQ-OV28. Results: No dose-limiting toxicities, CRS, or ICANS were observed; DCR was 80%. Conclusions: KT127 showed a manageable safety profile and preliminary biological activity in platinum-resistant advanced ovarian cancer, including heavily pretreated patients.

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DOI: 10. 1002/cncr.70279 ORIGINAL ARTICLE T-cell receptor—like chimeric antigen receptor T cells targeting mesothelin: A first-in-human dose-escalation trial for platinum-resistant advanced ovarian cancer Yiyang Shan MD1 | Bo Ding MD 1,2 | Feng Ji PhD2,3 | Hao Lin PhD1,2,3 | Weiwei Shi PhD1,2 | Enxiu Wang PhD4,5,6,7 | Chen Wang PhD4 | Yang Shen PhD1,2 1Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China 2Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine, Nanjing, China 3Department of Clinical Science and Research, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China 4Nanjing CART Medical Technology Co., Ltd, Nanjing, China 5Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China 6Clinical Pathological Diagnosis & Research Center, Youjiang Medical University for Nationalities, Baise, China 7The Key Laboratory of Molecular Pathology (Hepatobiliary Diseases) of Guangxi, Baise, China Correspondence Yang Shen, Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine, Nanjing, China. Email: [shenyang@seu.edu.cn](shenyang@seu.edu.cn) Funding information Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital, Grant/Award Numbers: 2023GSPKY11, GSP-LCYJFH01; National Clinical Key Discipline Construction Funds, Grant/Award Number: czxm-zk-40; National Natural Science Foundation of China, Grant/ Award Numbers: 82372126, 82072078; Major Science and Technology Projects (Life and Health) in Nanjing City, Grant/Award Number: 202305039; China Postdoctoral Science Foundation, Grant/Award Numbers: 2024M750460, 2023M740616; Nanjing Postdoctoral Research Foundation Project, Grant/Award Number: FTJ-bh-2; Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds, Grant/Award Abstract Background: Ovarian cancer remains a formidable therapeutic challenge due to late diagnosis, high recurrence rates, and limited treatment options. 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-cell receptor (TCR)-like chimeric antigen receptor (CAR) T-cell therapy targeting MSLN, designated KT127. Methods: A first-in-human, dose-escalation trial of KT127 was conducted following preclinical evaluation in vitro and in vivo. A combination of rapid titration and a standard “3 + 3” dose-escalation design was implemented. Eleven patients received KT127 at doses ranging from 1 × 106 to 2 × 107 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-free survival as efficacy measures. Quality of life (QOL) was assessed using the European Organisation for Research and Treatment of Cancer QLQ-OV28 questionnaire. Results: No dose-limiting toxicities, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome were observed. The DCR was 80%(95% confidence interval, 44.4%–97.5%). QOL assessments indicated improvement in | [This study is registered at](This study is registered at ClinicalTrials.gov)[ ClinicalTrials.gov](This study is registered at ClinicalTrials.gov) (Identifier: NCT05963100).
Yiyang Shan, Bo Ding and Feng Ji contributed equally to this article. | | --- | | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2026

FAQs

What is KT127 and what target does it address?

KT127 is a T-cell receptor—like CAR T-cell therapy designed to target mesothelin (MSLN), which is highly expressed in ovarian cancer.

How was the first-in-human dose-escalation trial conducted?

The trial used preclinical evaluation followed by a first-in-human, dose-escalation approach with rapid titration and a standard 3 + 3 design after lymphodepletion.

What were the primary safety outcomes observed with KT127?

The study reported no dose-limiting toxicities and no observed cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).

What efficacy-related signals were reported as secondary outcomes?

Secondary measures included disease control rate and survival outcomes; the reported disease control rate was 80% (with a 95% confidence interval of 44.4%–97.5%).

Sep 22, 2026

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