肿瘤细胞治疗研究
英文原题：EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors.
这些数据表明 EpCAM-CAR-T 治疗的可行性与耐受性。
CAR-T细胞治疗实体瘤的疗效尚不理想。EpCAM是上皮性肿瘤的生物标志物，但靶向EpCAM的CAR-T临床可行性尚未确立。本文报告EpCAM-CAR-T治疗实体瘤的临床前和临床研究。我们证明，经Dectin-1共刺激的EpCAM-CAR-T在异种移植小鼠模型及EpCAM人源化小鼠中具有强效抗肿瘤活性，且未见不良反应。值得注意的是，在上皮性肿瘤临床试验（NCT02915445）中，12名入组患者有6名（50%）出现可自行缓解的1/2级毒性，1名患者（8.3%）出现可逆的3级白细胞减少，未报告更高级别毒性。疗效分析显示，2名患者达到部分缓解。3名患者无进展生存超过23个月，其中1名患者达到2年无进展生存，且输注后第200天仍可检测到CAR-T细胞。这些数据表明EpCAM-CAR-T疗法具有可行性且耐受性良好。
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.
MEMBER ACCOUNT
登录成功会直接打开下一页。
