title: Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM.
abstract: BACKGROUND
  Adoptive transfer of tumor infiltrating or circulating lymphocytes transduced with tumor antigen receptors has been examined in various clinical trials to treat human cancers. The tumor antigens targeted by transferred lymphocytes affects the efficacy of this therapeutic approach. Because cancer stem cells (CSCs) play an important role in tumor growth and metastasis, we hypothesized that adoptive transfer of T cells targeting a CSC antigen could result in dramatic anti-tumor effects.
  
  
  RESULTS
  An EpCAM-specific chimeric antigen receptor (CAR) was constructed to transduce human peripheral blood lymphocytes (PBLs) and thereby enable them to target the CSC marker EpCAM. To investigate the therapeutic capabilities of PBLs expressing EpCAM-specific CARs, we used two different tumor models, PC3, the human prostate cancer cell line, which has low expression levels of EpCAM, and PC3M, a highly metastatic clone of PC3 that has high expression levels of EpCAM. We demonstrate that CAR-expressing PBLs can kill PC3M tumor cells in vitro and in vivo. Despite the low expression of EpCAM on PC3 cells, CAR-expressing PBLs significantly inhibited tumor growth and prolonged mouse survival in a PC3 metastasis model, probably by targeting the highly proliferative and metastatic population of cancer cells.
  
  
  CONCLUSIONS
  Our data demonstrate that PBLs expressing with EpCAM-specific CARs have significant anti-tumor activity against prostate cancer. Therefore, the adoptive transfer of T cells targeting EpCAM could have great potential as a cancer treatment.
authors: Department of Immunology, Cancer Hospital & Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. dengzhenling1985@126.com.
authors: Zhenling
authors: Z
authors: Deng
authors: Department of Immunology, Cancer Hospital & Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. wuyanhong849@126.com.
authors: Yanhong
authors: Y
authors: Wu
authors: Department of Immunology, Cancer Hospital & Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. wbma0702@163.com.
authors: Wenbo
authors: W
authors: Ma
authors: Department of Immunology, Cancer Hospital & Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. zhangsr@cicams.ac.cn.
authors: Shuren
authors: S
authors: Zhang
authors: Department of Immunology, Cancer Hospital & Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China. yqzhang.cams@gmail.com.
authors: Yu-Qian
authors: YQ
authors: Zhang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
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