Abstract 6316: Exploring the resistant mechanism of CAR T cell therapy targeting CLDN18.2 by single-cell sequencing

Abstract

Abstract Chimeric antigen receptor T cell (CAR T) therapy has achieved remarkable success in treating hematological malignancies but still faces overwhelming challenges for solid tumors. Our previous clinical trial (NCT03874897) has demonstrated promising results in patients with advanced CLDN18.2-positive gastric after receiving CT041 CAR T cell product. Though the disease control rate (DCR) reached 73% in 37 patients, it was unclear who would benefit from this therapy. Here in this study, we dynamically collected peripheral blood and ascites samples from 5 patients in this clinical trial before and at 3 and 7 days after the infusion of CT041, respectively. Utilizing single-cell sequencing analysis, we found that patients with a high proportion of naive-like T cells were more likely to benefit from CT041. Furthermore, we discovered that the high expression of CLDN18 in the ascites epithelial cells was correlated with a favorable prognosis, while ascites epithelial cells showing high MYC expression and the strong interaction between tumor cells and T cells were identified as adverse prognostic factors for CT041 treatment. These findings may provide theoretical evidence for subsequent screening of CAR T cell therapy benefitable population and improving the efficacy of CAR T cell therapy. Citation Format: Mingyang Ma, Changsong Qi, Chang Liu, Lei Jiang, Min Tao, Dan Liu, Panpan Zhang, Zhi Peng, Xiaotian Zhang, Jifang Gong, Yang Chen, Chunhong Zheng, Mi Deng, Lin Shen. Exploring the resistant mechanism of CAR T cell therapy targeting CLDN18.2 by single-cell sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6316.