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Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer.
Zhang, Bing-Lan; Li, Dan; Gong, You-Ling; Huang, Yong; Qin, Di-Yuan; Jiang, Lin; Liang, Xiao; Yang, Xiao; Gou, Hong-Feng; Wang, Yong-Sheng; Wei, Yu-Quan; Wang, Wei.
Afiliación
  • Zhang BL; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Li D; 2 Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
  • Gong YL; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Huang Y; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Qin DY; 3 Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Jiang L; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Liang X; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Yang X; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Gou HF; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Wang YS; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Wei YQ; 4 Department of Medical Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
  • Wang W; 1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
Hum Gene Ther ; 30(4): 402-412, 2019 04.
Article en En | MEDLINE | ID: mdl-30693795
ABSTRACT
Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. The study demonstrated that EpCAM CAR-T cells can elicit lytic cytotoxicity to target cells in an EpCAM-dependent manner and secrete cytotoxic cytokines, including interferon gamma and tumor necrosis factor alpha. Furthermore, adoptive transfer of EpCAM CAR-T cells significantly delayed tumor growth and formation in xenograft models. In addition, the safety evaluation showed that CAR-T cells have no systemic toxicity in mice. The data confirmed the antitumor ability and safety of CAR-T cells targeting EpCAM and may provide a new target for CAR-T cell therapies in treating solid tumors.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Linfocitos T / Neoplasias Colorrectales / Inmunoterapia Adoptiva / Molécula de Adhesión Celular Epitelial / Receptores Quiméricos de Antígenos Tipo de estudio: Prognostic_studies Idioma: En Revista: Hum Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2019 Tipo del documento: Article
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Linfocitos T / Neoplasias Colorrectales / Inmunoterapia Adoptiva / Molécula de Adhesión Celular Epitelial / Receptores Quiméricos de Antígenos Tipo de estudio: Prognostic_studies Idioma: En Revista: Hum Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2019 Tipo del documento: Article