E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor.

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

• Publication year

  2002

• Venue

  Molecular Therapy

• Publication date

  2002-05-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1006/MTHE.2002.0589PMID 11991754
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro

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• Gene therapy: a molecular approach to cancer treatment.

  2000cited by this paper
• A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer

  2000cited by this paper
• Targeting adenovirus

  2000cited by this paper
• Evaluation of E1-mutant adenoviruses as conditionally replicating agents for cancer therapy.

  2000cited by this paper
• Immunological Gene Therapy with ex Vivo Gene-Modified Tumor Cells: A Critique and a Reappraisal

  2000cited by this paper
• Evaluation of HSV-tk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes.

  2000cited by this paper
• An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy

  2000cited by this paper
• Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: role of gap-junctional intercellular communication.

  2000cited by this paper
• Replication-selective oncolytic adenoviruses: virotherapy aimed at genetic targets in cancer

  2000cited by this paper
• The Replicative Capacities of Large E1B-Null Group A and Group C Adenoviruses Are Independent of Host Cell p53 Status

  1999cited by this paper
• A Novel Tumor-Specific Replication-Restricted Adenoviral Vector for Gene Therapy of Hepatocellular Carcinoma

  1999cited by this paper
• Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

  1999cited by this paper
• Rising incidence of hepatocellular carcinoma in the United States.

  1999cited by this paper
• The increasing incidence of hepatocellular carcinoma.

  1999cited by this paper
• p53-Independent and -Dependent Requirements for E1B-55K in Adenovirus Type 5 Replication

  1999cited by this paper
• B7‐1 (CD80)‐gene transfer combined with interleukin‐12 administration elicits protective and therapeutic immunity against mouse hepatocellular carcinoma

  1999cited by this paper
• A Phase I/II Study of Hepatic Artery Infusion with wtp53-CMV-Ad in Metastatic Malignant Liver Tumours

  1999cited by this paper
• Rising Incidence of Hepatocellular Carcinoma in the United States

  1999cited by this paper
• Induction of Transformation and p53-Dependent Apoptosis by Adenovirus Type 5 E4orf6/7 cDNA

  1999cited by this paper
• A Novel Strategy of Cell Targeting Based on Tissue-Specific Expression of the Ecotropic Retrovirus Receptor Gene

  1998influential reference
• Trends in primary liver cancer.

  1998cited by this paper
• An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa tumor necrosis factor (TNF) receptor gene transfection and mutein TNF administration.

  1998cited by this paper
• Retrovirus-mediated gene therapy for hepatocellular carcinoma: selective and enhanced suicide gene expression regulated by human alpha-fetoprotein enhancer directly linked to its promoter.

  1998cited by this paper
• Replication of ONYX-015, a Potential Anticancer Adenovirus, Is Independent of p53 Status in Tumor Cells

  1998cited by this paper
• Immune Response to Recombinant Capsid Proteins of Adenovirus in Humans: Antifiber and Anti-Penton Base Antibodies Have a Synergistic Effect on Neutralizing Activity

  1998cited by this paper
• Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins

  1997cited by this paper
• In vivo gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by adenovirus-mediated transfer of cytosine deaminase gene.

  1997cited by this paper
• Integrin-mediated transfection with peptides containing arginine-glycine-aspartic acid domains

  1997cited by this paper
• Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to paclitaxel (Taxol) by adenovirus type 5 E1A

  1997cited by this paper
• Pre-existing immunity to adenovirus does not prevent tumor regression following intratumoral administration of a vector expressing IL-12 but inhibits virus dissemination

  1997cited by this paper
• ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents

  1997cited by this paper
• Gene therapy for α‐fetoprotein‐producing human hepatoma cells by adenovirus‐mediated transfer of the herpes simplex virus thymidine kinase gene

  1996cited by this paper
• Long Term Correction of Bilirubin-UDP-glucuronosyltransferase Deficiency in Gunn Rats by Administration of a Recombinant Adenovirus during the Neonatal Period*

  1996cited by this paper
• An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells

  1996cited by this paper
• Regulated expression of artificial chimeric genes contained in retroviral vectors: implications for virus-directed enzyme prodrug therapy (VDEPT) and other gene therapy applications.

  1996cited by this paper
• Transfection of glutathione S-transferase (GST)-pi antisense complementary DNA increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide.

  1996cited by this paper
• Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits long-term gene therapy in Gunn rats.

  1996cited by this paper
• Circumventing the immune response to adenovirus-mediated gene therapy.

  1996cited by this paper
• The adenovirus death protein (E3-11.6K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells

  1996cited by this paper
• Therapy of unresectable hepatocellular carcinoma.

  1995cited by this paper
• Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter.

  1995cited by this paper
• Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents

  1995cited by this paper
• Liver-directed gene therapy: prospects and problems.

  1994cited by this paper
• Packaging capacity and stability of human adenovirus type 5 vectors

  1993cited by this paper
• A position-dependent silencer plays a major role in repressing alpha-fetoprotein expression in human hepatoma

  1991cited by this paper
• Adenovirus E1A under the control of heterologous promoters: wide variation in E1A expression levels has little effect on virus replication.

  1990cited by this paper
• Progress toward human gene therapy.

  1989cited by this paper
• Cell-specific enhancer activity in a far upstream region of the human alpha-fetoprotein gene.

  1987cited by this paper
• Mutational analysis of the adenovirus E1a gene: the role of transcriptional regulation in transformation.

  1987cited by this paper
• Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection.

  1987cited by this paper
• Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells

  1986cited by this paper
• Adenovirus type 5 early region 1b gene product is required for efficient shutoff of host protein synthesis

  1984cited by this paper

• Understanding Gene Involvement in Hepatocellular Carcinoma: Implications for Gene Therapy and Personalized Medicine

  2024cites this paper
• The future of interleukin gene therapy in head and neck cancers

  2024cites this paper
• Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of AFP-Related Liver Cancer

  2022cites this paper
• Targeting telomerase for its advent in cancer therapeutics.

  2020cites this paper
• Somatostatin Receptor Based Imaging and Radionuclide Therapy

  2015cites this paper
• Cancer Gene Therapy

  2015cites this paper
• Alpha-Fetoprotein Promoter-Driven Cre/LoxP-Switched RNA Interference for Hepatocellular Carcinoma Tissue-Specific Target Therapy

  2013cites this paper
• Potent antitumoral effects of targeted promoter-driven oncolytic adenovirus armed with Dm-dNK for breast cancer in vitro and in vivo.

  2013cites this paper
• Regression of hepatocarcinoma cells using RNA aptamer specific to alpha-fetoprotein.

  2012cites this paper
• Gene therapy in liver diseases: state-of-the-art and future perspectives.

  2012cites this paper
• Antitumor effects of bladder cancer-specific adenovirus carrying E1A-androgen receptor in bladder cancer

  2012cites this paper
• In vivo bioluminescent imaging of α‐fetoprotein‐producing hepatocellular carcinoma in the diethylnitrosamine‐treated mouse using recombinant adenoviral vector

  2012cites this paper
• Recent advances in oncolytic virus design

  2011cites this paper
• Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL

  2011cites this paper
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  2011cites this paper
• Targeted hepatocellular carcinoma proapoptotic BikDD gene therapy

  2011cites this paper
• Gene therapy of liver cancer: an update

  2011cites this paper
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  2011cites this paper
• Cancer Therapy: Preclinical A Hypoxia- and a -Fetoprotein – Dependent Oncolytic Adenovirus Exhibits Specific Killing of Hepatocellular Carcinomas

  2010cites this paper
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  2009cites this paper
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  2009cites this paper
• Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication‐competent CD95L adenovirus

  2009cites this paper
• Experimental models of hepatocellular carcinoma: developments and evolution

  2009influential citation
• Strategies for Successful Vaccination against Hepatocellular Carcinoma

  2009cites this paper
• Oncolytic adenovirus delivering herpes simplex virus thymidine kinase suicide gene reduces the growth of human retinoblastoma in an in vivo mouse model.

  2009cites this paper
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  2008cites this paper
• Potent anti-hepatoma efficacy of HCCS1 via dual tumor-targeting gene-virotherapy strategy.

  2008cites this paper
• Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53, and 5‐fluorouracil in mice

  2008cites this paper
• Advances in experimental and translational research in the treatment of hepatocellular carcinoma.

  2008cites this paper
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  2007cites this paper
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  2007cites this paper
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  2006cites this paper
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  2006cites this paper
• Selective replication of E1B55K-deleted adenoviruses depends on enhanced E1A expression in cancer cells

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  2006cites this paper
• Gene therapy of liver cancer.

  2006cites this paper
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  2006cites this paper
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  2006cites this paper
• Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma.

  2005cites this paper
• Replication-selective oncolytic viruses in the treatment of cancer

  2005cites this paper
• Cancer Gene Therapy

  2005cites this paper
• Development of Oncolytic Adenoviruses

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  2005cites this paper
• Replication-selective oncolytic viruses in the treatment of cancer

  2005cites this paper
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  2005cites this paper
• Gene Therapy and Virotherapy of Gastric Cancer: Preclinical Results and Clinical Developments

  2005cites this paper
• Transcriptionally targeted adenovirus vectors.

  2005cites this paper
• Telomerase-dependent virotherapy overcomes resistance of hepatocellular carcinomas against chemotherapy and tumor necrosis factor-related apoptosis-inducing ligand by elimination of Mcl-1.

  2005cites this paper
• Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter.

  2004cites this paper
• Gene Therapy with Secretory Leukoprotease Inhibitor Promoter-Controlled Replication-Competent Adenovirus for Non-Small Cell Lung Cancer

  2004cites this paper
• Non-Small Cell Lung Cancer Promoter-Controlled Replication-Competent Adenovirus for Gene Therapy with Secretory Leukoprotease Inhibitor

  2004cites this paper
• Preparation and characteristics of DNA-nanoparticles targeting to hepatocarcinoma cells.

  2004cites this paper
• Gene therapy of liver diseases

  2004cites this paper
• Transcriptionally targeted gene therapy to detect and treat cancer.

  2003cites this paper
• Medikamentöse Therapie des hepatozellulären Karzinoms

  2003cites this paper
• Cancer Gene Therapy

  2003cites this paper
• A novel tetracycline-controlled transactivator–transrepressor system enables external control of oncolytic adenovirus replication

  2003cites this paper
• [Systemic treatment for hepatocellular carcinoma].

  2003cites this paper
• Telomerase-dependent oncolytic adenovirus for cancer treatment

  2003cites this paper
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  2003cites this paper
• Selectively replicating oncolytic adenoviruses as cancer therapeutics.

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