title: Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma.
abstract: OBJECTIVE
  The aim of our study is to elucidate whether T cells expressing GPC3-targeted chimeric antigen receptor (CAR) can efficiently eliminate GPC3-positive HCC cells and their potential in the treatment of HCC.
  
  
  METHODS
  T cells expressing a first-generation and third-generation GPC3-targeted CAR were prepared using lentiviral vector transduction. The in vitro and in vivo cytotoxic activities of the genetically engineered CAR T cells were evaluated against various HCC cell lines.
  
  
  RESULTS
  GPC3-targeted CAR T cells could efficiently kill GPC3-positive HCC cells but not GPC3-negative cells in vitro. These cytotoxic activities seemed to be positively correlated with GPC3 expression levels in the target cells. In addition, T cells expressing the third-generation GPC3-targeted CAR could eradicate HCC xenografts with high level of GPC3 expression and efficiently suppress the growth of HCC xenografts with low GPC3 expression level in vivo. The survival of the mice bearing established orthotopic Huh-7 xenografts was significantly prolonged by the treatment with the third-generation GPC3-targeted CAR T cells.
  
  
  CONCLUSIONS
  GPC3-targeted CAR T cells could potently eliminate GPC3-positive HCC cells, thereby providing a promising therapeutic intervention for GPC3-positive HCC.
authors.affiliation: Medical School of Fudan University, Shanghai, China. State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Kesang
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Bizhi
authors.initials: B
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China. National Center for Liver Cancer, Shanghai, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Zonghaili@shsmu.edu.cn.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D053673:Glypicans / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D061905:Single-Domain Antibodies / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D053673:Glypicans; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D061905:Single-Domain Antibodies