RRC ID 72590
Author Gao H, Li K, Tu H, Pan X, Jiang H, Shi B, Kong J, Wang H, Yang S, Gu J, Li Z.
Title Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma.
Journal Clin Cancer Res
Abstract PURPOSE: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.
EXPERIMENTAL DESIGN: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.
Volume 20(24)
Pages 6418-28
Published 2014-12-15
DOI 10.1158/1078-0432.CCR-14-1170
PII 1078-0432.CCR-14-1170
PMID 25320357
MeSH Animals Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / immunology* Carcinoma, Hepatocellular / mortality Carcinoma, Hepatocellular / pathology* Carcinoma, Hepatocellular / therapy Cell Line, Tumor Cytokines / biosynthesis Cytotoxicity, Immunologic Disease Models, Animal Gene Order Genetic Vectors / genetics Glypicans / immunology* Humans Immunotherapy Lentivirus / genetics Liver Neoplasms / genetics Liver Neoplasms / immunology* Liver Neoplasms / mortality Liver Neoplasms / pathology* Liver Neoplasms / therapy Mice Receptors, Antigen, T-Cell / genetics Recombinant Fusion Proteins / genetics Single-Domain Antibodies / genetics Single-Domain Antibodies / immunology T-Cell Antigen Receptor Specificity / genetics T-Cell Antigen Receptor Specificity / immunology T-Lymphocyte Subsets / immunology* T-Lymphocyte Subsets / metabolism T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Cytotoxic / metabolism Transduction, Genetic Tumor Burden / immunology Xenograft Model Antitumor Assays
IF 10.107
Human and Animal Cells HuH-7