Anti‐PD‐1 Nanobody‐Armored MSLN CAR‐T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: Malignant mesothelioma (MM) is an aggressive and currently incurable cancer with limited therapeutic options. Due to the high expression of mesothelin in this cancer, anti‐PD‐1 nanobody‐armored mesothelin‐targeting CAR‐T (NAC‐T) cells are developed. Based on the enhanced anti‐tumor activity observed in preclinical in vitro and in vivo studies, a first‐in‐human clinical trial is initiated. Eleven patients with malignant mesothelioma who have progressed after standard therapies receive intravenous infusions of 5–20 × 10 6 per kg NAC‐T cells following lymphodepletion. The treatment is well tolerated, with no dose‐limiting toxicity observed. The overall response rate is 63.6%, including one complete response, and the disease control rate is 100%. The median progression‐free survival is 5.0 months, and the median overall survival is 25.6 months. Moreover, T cell receptor and single‐cell sequencing analyses in patients with varying responses revealed specific clonal expansion of T cell subtypes and enhanced reactivity to tumor‐associated antigens. These findings suggest that NAC‐T cell therapy represents a promising therapeutic strategy for patients with malignant mesothelioma.
Source: Advanced Science
Authors: Yan Sun, Haochen Yang, Qing Xu, Xingya Li, Jinxing Lou, Jianchun Duan, Jiachen Xu, Zhuqing Liu, Yong Xia, Zhicai Lin, Linlin Li, Dan Sun, Jiaguo Li, Tao Liu, Jun Guo, Wenfeng Xu, Weimin Zhu, Yi Liu, Boyang Sun, Jia Zhong, Lijie Rong, Qijun Qian, Chenqi Xu, Jie Wang
Institutions: Shanghai University, Chinese Academy of Sciences, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, State Key Laboratory of Molecular Biology, Tongji University, Shanghai Tenth People's Hospital, First Affiliated Hospital of Zhengzhou University, Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,730
Awards: G2630851322, G5124162788, G6469481620
OpenAlex ID: W4415512896