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

• Published in: Journal of Veterinary Medical Science Vol. 83; no. 2; pp. 241 - 247
• Main Authors: FU, Juan, SHANG, Yuhong, QIAN, Zhang, HOU, Jinping, YAN, Feng, LIU, Guodi, DEHUA, Li, TIAN, Xiaoli
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 2021; The Japanese Society of Veterinary Science
• Subjects: Animals; Cell Line, Tumor; chimeric antigen receptor T cells; Epithelial Cell Adhesion Molecule; Female; immunodeficient mice; Immunology; immunotherapy; Immunotherapy, Adoptive - veterinary; Mice; ovarian cancer; Ovarian Neoplasms - therapy; Ovarian Neoplasms - veterinary; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Xenograft Model Antitumor Assays - veterinary; immunodeficient mice; chimeric antigen receptor T cells; ovarian cancer; immunotherapy; epithelial cell adhesion molecule
• ISSN: 0916-7250; 1347-7439; 1347-7439
• DOI: 10.1292/jvms.20-0455

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.