Exploring the therapeutic efficacy difference in claudin18.2-targeted cell therapy revealed by single-cell sequencing

作者：Mingyang Ma, Chang Liu, Lei Jiang, Dan Liu, Panpan Zhang, Min Tao, Miao Zhang, Jifang Gong, Zhi Peng, Xiaotian Zhang, Jian Li, Chunhong Zheng, Mi Deng, Lin Shen, Changsong Qi · 发表于：iScience · 年份：2025 · DOI：10.1016/j.isci.2025.111768 · 被引用次数：8 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Single-cell and spatial transcriptomics

Chimeric antigen receptor T cell (CAR T) therapy has been successfully used to treat hematological malignancies. Nonetheless, its application to solid tumors remains challenging. Our previous analysis of the ongoing clinical trial (NCT03874897) demonstrated promising results in patients with advanced CLDN18.2-positive gastric cancer who received CT041 CAR T treatment. Here, we collected peripheral blood and ascites from five patients from the clinical trial 3 and 7 days (d) after CT041 infusion. Patients with a high proportion of naïve-like T cells were more likely to benefit from CT041 treatment. We found that high expression of CLDN18 in ascites epithelial cells correlated with a favorable prognosis, whereas ascites epithelial cells with high MYC expression and strong interactions between tumor cells and T cells were adverse prognostic factors for CT041 treatment. These findings may provide theoretical evidence for the screening of populations that can benefit from CAR T therapy and improve the efficacy of CAR T therapy.