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Enhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells

Dendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs tr... Full description

Journal Title: Molecular medicine reports 2015-05, Vol.11 (5), p.3361-3367
Main Author: WANG, YULIANG
Other Authors: WANG, YINLONG , MU, HONG , LIU, TAO , CHEN, XIAOBO , SHEN, ZHONGYANG
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Greece: D.A. Spandidos
ID: ISSN: 1791-2997
Link: https://www.ncbi.nlm.nih.gov/pubmed/25625609
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4368068
title: Enhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells
format: Article
creator:
  • WANG, YULIANG
  • WANG, YINLONG
  • MU, HONG
  • LIU, TAO
  • CHEN, XIAOBO
  • SHEN, ZHONGYANG
subjects:
  • Adoptive immunotherapy
  • Animals
  • Antigen (tumor-associated)
  • Antitumor agents
  • Articles
  • Biotechnology
  • Cancer therapies
  • Carcinoma, Hepatocellular - genetics
  • Carcinoma, Hepatocellular - immunology
  • Carcinoma, Hepatocellular - pathology
  • Cell Line, Tumor
  • Coculture Techniques
  • cytokine
  • cytokine-induced killer cells
  • Cytokine-Induced Killer Cells - immunology
  • Cytokine-Induced Killer Cells - metabolism
  • Cytotoxicity
  • Cytotoxicity, Immunologic
  • Dendritic cells
  • Dendritic Cells - immunology
  • Dendritic Cells - metabolism
  • Disease Models, Animal
  • Effector cells
  • Flow cytometry
  • Genes
  • Genetic aspects
  • glypican 3
  • Glypicans - genetics
  • GPC3 gene
  • Green fluorescent protein
  • Heparan sulfate proteoglycans
  • Hepatocellular carcinoma
  • Hepatoma
  • Humans
  • Immunogenicity
  • Immunomodulation
  • Immunotherapy
  • induced killer cells
  • Interferon-gamma - biosynthesis
  • Killer cells
  • Liver cancer
  • Liver Neoplasms - genetics
  • Liver Neoplasms - immunology
  • Liver Neoplasms - pathology
  • Medical research
  • Mice
  • Phenotype
  • Physiological aspects
  • Research
  • Studies
  • T cell receptors
  • Transduction, Genetic
  • Transfection
  • Xenograft Model Antitumor Assays
  • γ-Interferon
ispartof: Molecular medicine reports, 2015-05, Vol.11 (5), p.3361-3367
description: Dendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs transduced with the GPC3 gene (DCs-GPC3) and co-cultured with autologous cytokine-induced killer cells (CIKs) may induce a marked specific immune response against GPC3-expressing HCC cells in vitro and in vivo. Human DCs were transfected with a green fluorescent protein plasmid with GPC3 by nucleofection and then co-cultured with autologous CIKs. Flow cytometry was used to measure the phenotypes of DCs and CIKs. The co-cultured cells were harvested and incubated with HCC cells and the cytotoxicity of the CIKs was assessed by nonradioactive cytotoxicity assay. The anti-tumor activity of these effector cells was further evaluated using a nude mouse tumor model. The results demonstrated that DCs-GPC3 significantly promoted the autologous CIKs differentiation, as well as anti-tumor cytokine interferon-γ secretion. In addition, DCs-GPC3-CIKs significantly enhanced the cytotoxic activity against GPC3-expressing HepG2 cells, indicating a GPC3-specific marked immune response against HCC cells. The in vivo data indicated that DCs-GPC3-CIKs exhibited significant HepG2 cell-induced tumor growth inhibition in nude mice. The results of the present study provided a new insight into the design of personalizing adoptive immunotherapy for GPC3-expressing HCC cells.
language: eng
source:
identifier: ISSN: 1791-2997
fulltext: no_fulltext
issn:
  • 1791-2997
  • 1791-3004
url: Link


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titleEnhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells
creatorWANG, YULIANG ; WANG, YINLONG ; MU, HONG ; LIU, TAO ; CHEN, XIAOBO ; SHEN, ZHONGYANG
creatorcontribWANG, YULIANG ; WANG, YINLONG ; MU, HONG ; LIU, TAO ; CHEN, XIAOBO ; SHEN, ZHONGYANG
descriptionDendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs transduced with the GPC3 gene (DCs-GPC3) and co-cultured with autologous cytokine-induced killer cells (CIKs) may induce a marked specific immune response against GPC3-expressing HCC cells in vitro and in vivo. Human DCs were transfected with a green fluorescent protein plasmid with GPC3 by nucleofection and then co-cultured with autologous CIKs. Flow cytometry was used to measure the phenotypes of DCs and CIKs. The co-cultured cells were harvested and incubated with HCC cells and the cytotoxicity of the CIKs was assessed by nonradioactive cytotoxicity assay. The anti-tumor activity of these effector cells was further evaluated using a nude mouse tumor model. The results demonstrated that DCs-GPC3 significantly promoted the autologous CIKs differentiation, as well as anti-tumor cytokine interferon-γ secretion. In addition, DCs-GPC3-CIKs significantly enhanced the cytotoxic activity against GPC3-expressing HepG2 cells, indicating a GPC3-specific marked immune response against HCC cells. The in vivo data indicated that DCs-GPC3-CIKs exhibited significant HepG2 cell-induced tumor growth inhibition in nude mice. The results of the present study provided a new insight into the design of personalizing adoptive immunotherapy for GPC3-expressing HCC cells.
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languageeng
publisherGreece: D.A. Spandidos
subjectAdoptive immunotherapy ; Animals ; Antigen (tumor-associated) ; Antitumor agents ; Articles ; Biotechnology ; Cancer therapies ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - immunology ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Coculture Techniques ; cytokine ; cytokine-induced killer cells ; Cytokine-Induced Killer Cells - immunology ; Cytokine-Induced Killer Cells - metabolism ; Cytotoxicity ; Cytotoxicity, Immunologic ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Disease Models, Animal ; Effector cells ; Flow cytometry ; Genes ; Genetic aspects ; glypican 3 ; Glypicans - genetics ; GPC3 gene ; Green fluorescent protein ; Heparan sulfate proteoglycans ; Hepatocellular carcinoma ; Hepatoma ; Humans ; Immunogenicity ; Immunomodulation ; Immunotherapy ; induced killer cells ; Interferon-gamma - biosynthesis ; Killer cells ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - immunology ; Liver Neoplasms - pathology ; Medical research ; Mice ; Phenotype ; Physiological aspects ; Research ; Studies ; T cell receptors ; Transduction, Genetic ; Transfection ; Xenograft Model Antitumor Assays ; γ-Interferon
ispartofMolecular medicine reports, 2015-05, Vol.11 (5), p.3361-3367
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3Copyright © 2015, Spandidos Publications 2015
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0WANG, YULIANG
1WANG, YINLONG
2MU, HONG
3LIU, TAO
4CHEN, XIAOBO
5SHEN, ZHONGYANG
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0Enhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells
1Molecular medicine reports
addtitleMol Med Rep
descriptionDendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs transduced with the GPC3 gene (DCs-GPC3) and co-cultured with autologous cytokine-induced killer cells (CIKs) may induce a marked specific immune response against GPC3-expressing HCC cells in vitro and in vivo. Human DCs were transfected with a green fluorescent protein plasmid with GPC3 by nucleofection and then co-cultured with autologous CIKs. Flow cytometry was used to measure the phenotypes of DCs and CIKs. The co-cultured cells were harvested and incubated with HCC cells and the cytotoxicity of the CIKs was assessed by nonradioactive cytotoxicity assay. The anti-tumor activity of these effector cells was further evaluated using a nude mouse tumor model. The results demonstrated that DCs-GPC3 significantly promoted the autologous CIKs differentiation, as well as anti-tumor cytokine interferon-γ secretion. In addition, DCs-GPC3-CIKs significantly enhanced the cytotoxic activity against GPC3-expressing HepG2 cells, indicating a GPC3-specific marked immune response against HCC cells. The in vivo data indicated that DCs-GPC3-CIKs exhibited significant HepG2 cell-induced tumor growth inhibition in nude mice. The results of the present study provided a new insight into the design of personalizing adoptive immunotherapy for GPC3-expressing HCC cells.
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0Adoptive immunotherapy
1Animals
2Antigen (tumor-associated)
3Antitumor agents
4Articles
5Biotechnology
6Cancer therapies
7Carcinoma, Hepatocellular - genetics
8Carcinoma, Hepatocellular - immunology
9Carcinoma, Hepatocellular - pathology
10Cell Line, Tumor
11Coculture Techniques
12cytokine
13cytokine-induced killer cells
14Cytokine-Induced Killer Cells - immunology
15Cytokine-Induced Killer Cells - metabolism
16Cytotoxicity
17Cytotoxicity, Immunologic
18Dendritic cells
19Dendritic Cells - immunology
20Dendritic Cells - metabolism
21Disease Models, Animal
22Effector cells
23Flow cytometry
24Genes
25Genetic aspects
26glypican 3
27Glypicans - genetics
28GPC3 gene
29Green fluorescent protein
30Heparan sulfate proteoglycans
31Hepatocellular carcinoma
32Hepatoma
33Humans
34Immunogenicity
35Immunomodulation
36Immunotherapy
37induced killer cells
38Interferon-gamma - biosynthesis
39Killer cells
40Liver cancer
41Liver Neoplasms - genetics
42Liver Neoplasms - immunology
43Liver Neoplasms - pathology
44Medical research
45Mice
46Phenotype
47Physiological aspects
48Research
49Studies
50T cell receptors
51Transduction, Genetic
52Transfection
53Xenograft Model Antitumor Assays
54γ-Interferon
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titleEnhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells
authorWANG, YULIANG ; WANG, YINLONG ; MU, HONG ; LIU, TAO ; CHEN, XIAOBO ; SHEN, ZHONGYANG
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0Adoptive immunotherapy
1Animals
2Antigen (tumor-associated)
3Antitumor agents
4Articles
5Biotechnology
6Cancer therapies
7Carcinoma, Hepatocellular - genetics
8Carcinoma, Hepatocellular - immunology
9Carcinoma, Hepatocellular - pathology
10Cell Line, Tumor
11Coculture Techniques
12cytokine
13cytokine-induced killer cells
14Cytokine-Induced Killer Cells - immunology
15Cytokine-Induced Killer Cells - metabolism
16Cytotoxicity
17Cytotoxicity, Immunologic
18Dendritic cells
19Dendritic Cells - immunology
20Dendritic Cells - metabolism
21Disease Models, Animal
22Effector cells
23Flow cytometry
24Genes
25Genetic aspects
26glypican 3
27Glypicans - genetics
28GPC3 gene
29Green fluorescent protein
30Heparan sulfate proteoglycans
31Hepatocellular carcinoma
32Hepatoma
33Humans
34Immunogenicity
35Immunomodulation
36Immunotherapy
37induced killer cells
38Interferon-gamma - biosynthesis
39Killer cells
40Liver cancer
41Liver Neoplasms - genetics
42Liver Neoplasms - immunology
43Liver Neoplasms - pathology
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48Research
49Studies
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51Transduction, Genetic
52Transfection
53Xenograft Model Antitumor Assays
54γ-Interferon
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atitleEnhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells
jtitleMolecular medicine reports
addtitleMol Med Rep
date2015-05
risdate2015
volume11
issue5
spage3361
epage3367
pages3361-3367
issn1791-2997
eissn1791-3004
notesContributed equally
abstractDendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs transduced with the GPC3 gene (DCs-GPC3) and co-cultured with autologous cytokine-induced killer cells (CIKs) may induce a marked specific immune response against GPC3-expressing HCC cells in vitro and in vivo. Human DCs were transfected with a green fluorescent protein plasmid with GPC3 by nucleofection and then co-cultured with autologous CIKs. Flow cytometry was used to measure the phenotypes of DCs and CIKs. The co-cultured cells were harvested and incubated with HCC cells and the cytotoxicity of the CIKs was assessed by nonradioactive cytotoxicity assay. The anti-tumor activity of these effector cells was further evaluated using a nude mouse tumor model. The results demonstrated that DCs-GPC3 significantly promoted the autologous CIKs differentiation, as well as anti-tumor cytokine interferon-γ secretion. In addition, DCs-GPC3-CIKs significantly enhanced the cytotoxic activity against GPC3-expressing HepG2 cells, indicating a GPC3-specific marked immune response against HCC cells. The in vivo data indicated that DCs-GPC3-CIKs exhibited significant HepG2 cell-induced tumor growth inhibition in nude mice. The results of the present study provided a new insight into the design of personalizing adoptive immunotherapy for GPC3-expressing HCC cells.
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