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

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 k...

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Autores principales: FU, Juan, SHANG, Yuhong, QIAN, Zhang, HOU, Jinping, YAN, Feng, LIU, Guodi, DEHUA, Li, TIAN, Xiaoli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Society of Veterinary Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972873/
https://www.ncbi.nlm.nih.gov/pubmed/33328392
http://dx.doi.org/10.1292/jvms.20-0455
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author FU, Juan
SHANG, Yuhong
QIAN, Zhang
HOU, Jinping
YAN, Feng
LIU, Guodi
DEHUA, Li
TIAN, Xiaoli
author_facet FU, Juan
SHANG, Yuhong
QIAN, Zhang
HOU, Jinping
YAN, Feng
LIU, Guodi
DEHUA, Li
TIAN, Xiaoli
author_sort FU, Juan
collection PubMed
description 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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spelling pubmed-79728732021-03-23 Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model FU, Juan SHANG, Yuhong QIAN, Zhang HOU, Jinping YAN, Feng LIU, Guodi DEHUA, Li TIAN, Xiaoli J Vet Med Sci Immunology 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. The Japanese Society of Veterinary Science 2020-12-17 2021-02 /pmc/articles/PMC7972873/ /pubmed/33328392 http://dx.doi.org/10.1292/jvms.20-0455 Text en ©2021 The Japanese Society of Veterinary Science This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Immunology
FU, Juan
SHANG, Yuhong
QIAN, Zhang
HOU, Jinping
YAN, Feng
LIU, Guodi
DEHUA, Li
TIAN, Xiaoli
Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model
title Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model
title_full Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model
title_fullStr Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model
title_full_unstemmed Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model
title_short Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model
title_sort chimeric antigen receptor-t (car-t) cells targeting epithelial cell adhesion molecule (epcam) can inhibit tumor growth in ovarian cancer mouse model
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972873/
https://www.ncbi.nlm.nih.gov/pubmed/33328392
http://dx.doi.org/10.1292/jvms.20-0455
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