EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors

作者：Dan Dan Li, Xianling Guo, Kun Yang, Yuening Yang, Weilin Zhou, Yong Huang, Xiao Liang, Jinhua Su, Lin Jiang, Jing Li, Maorong Fu, Haixia He, Jinrong Yang, Shi H, Hanshuo Yang, Aiping Tong, Nianyong Chen, Jian‐Kun Hu, Qing Xu, Yu-Quan Wei, Wei Wang · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.adg9721 · 被引用次数：89 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Nanowire Synthesis and Applications

The efficacy of CAR-T cells for solid tumors is unsatisfactory. EpCAM is a biomarker of epithelial tumors, but the clinical feasibility of CAR-T therapy targeting EpCAM is lacking. Here, we report pre- and clinical investigations of EpCAM-CAR-T cells for solid tumors. We demonstrated that EpCAM-CAR-T cells costimulated by Dectin-1 exhibited robust antitumor activity without adverse effects in xenograft mouse models and EpCAM-humanized mice. Notably, in clinical trials for epithelial tumors (NCT02915445), 6 (50%) of the 12 enrolled patients experienced self-remitted grade 1/2 toxicities, 1 patient (8.3%) experienced reversible grade 3 leukopenia, and no higher-grade toxicity reported. Efficacy analysis determined two patients as partial response. Three patients showed >23 months of progression-free survival, among whom one patient experienced 2-year progress-free survival with detectable CAR-T cells 200 days after infusion. These data demonstrate the feasibility and tolerability of EpCAM-CAR-T therapy.