Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model

靶向上皮细胞黏附分子(EpCAM)的嵌合抗原受体T细胞(CAR-T细胞)可抑制卵巢癌小鼠模型中的肿瘤生长。

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作者:Juan Fu,Yuhong Shang,Zhang Qian,Jinping Hou,Feng Yan,Guodi Liu,Li Dehua,Xiaoli Tian

Abstract

Ovarian cancer (OC) is one of the most lethal solid tumors with poor prognosis. In 2017, two chimeric antigen receptor-T (CAR-T) cell drugs were approved by the U.S. Food and Drug Administration (FDA), and continuously optimized CAR-T cells therapy might be the novel hope for OC patient. EpCAM are known to be over-expressed in OC cells and could be targeted by CAR-T cells. However, the feasibility of using EpCAM-CAR-T cells to treat OC still needs to be verified. We engineered the 3rd-generation EpCAM-CAR containing a single-chain variable fragment (scFv) EpCAM-scFv that targeting EpCAM, a CD8 transmembrane domain, the costimulatory domains from both CD28 and 4-1BB, and activating domain CD3ζ and then transduced the CAR into T-cells via lentivirus. In addition, the cytotoxicity and cytokine releasing ability of the EpCAM-CAR-T cells against OC cell SKOV3 were verified in vitro. The in vivo data also showed that EpCAM-CAR-T cells significantly reduced the tumor size in OC xenograft mouse models. The anti-tumor activity of EpCAM-CAR-T cells against OC in vitro and in vivo indicated that the CAR-T might provide a promising therapeutic approach to OC.

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