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

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.