Journal
JOURNAL OF VETERINARY MEDICAL SCIENCE
Volume 83, Issue 2, Pages 241-247Publisher
JAPAN SOC VET SCI
DOI: 10.1292/jvms.20-0455
Keywords
chimeric antigen receptor T cells; epithelial cell adhesion molecule; immunodeficient mice; immunotherapy; ovarian cancer
Categories
Funding
- Shanghai Science and Technology Committee (STCSM) [19ZR1454700]
- Dalian Science and Technology Innovation Foundation [2020JJ27SN097]
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CAR-T therapy is considered a new hope for treating ovarian cancer. Experimental results have shown that EpCAM-CAR-T cells have good cytotoxicity and in vivo anti-tumor activity against ovarian cancer.
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 CD3 sigma 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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