Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells.

Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS.

A clinical protocol to inhibit the HGF/c-Met pathway for malignant mesothelioma with an intrapleural injection of adenoviruses expressing the NK4 gene.

Background: The hepatocyte growth factor (HGF)/c-Met signal pathway is up-regulated in human mesothelioma and suppression of the HGF/c-Met signaling with a competitive inhibitor, NK4 homologous to HGF in the structure, produced anti-tumor effects to mesothelioma in a preclinical study. Mesothelioma is highly resistant to a number of chemotherapeutic agents but distant metastasis to extra-thoracic organs is relatively infrequent until the late stage.

Methods/design: We planned to conduct a clinical study of gene therapy with adenoviruses expressing the NK4 gene (Ad-NK4) to control the local tumor growth.

A combined lymphokine-activated killer (LAK) cell immunotherapy and adenovirus-p53 gene therapy for head and neck squamous cell carcinoma.

Background: The antitumor activity of lymphokine activated killer (LAK) cells immunotherapy is not always effective in all patients, especially when used alone. In this study, we investigated the in vitro antitumor activities of a combination of LAK immunotherapy and gene therapy employing an adenovirus carrying the p53 gene (Ad-p53) in human head and neck squamous cell carcinoma.

Materials And Methods: The in vitro cytotoxicity of LAK cells was tested in H891 cells infected with or without Ad-p53, and the mRNA expression levels of natural killer group 2D ligands (UL16 binding protein (ULBP) 1 to 5) and tumor necrosis factor (TNF-α) in these cells were measured by real-time reverse transcription polymerase chain reaction.

Oral administration of genetically modified Bifidobacterium displaying HCV-NS3 multi-epitope fusion protein could induce an HCV-NS3-specific systemic immune response in mice.

More than 170 million people worldwide are chronic HCV (Hepatitis C virus) carriers, and about 30% of them will develop progressive liver disease, such as cirrhosis and hepatocellular carcinoma. A combination of pegylated interferon-α with ribavirin, the standard treatment for HCV infection, has been effective in fewer than 50% of patients infected with HCV genotype 1. A strong T cell response against the nonstructural protein 3 (NS3) is important for recovery from acute HCV infection, and an early multi-specific CD4+ helper and CD8+ cytotoxic T cell response is critical for HCV clearance.

Gene silencing with siRNA targeting E6/E7 as a therapeutic intervention against head and neck cancer-containing HPV16 cell lines.

Conclusion: Our results indicate that siRNA E6 and/or E7 may have potential as a gene-specific therapy for human papillomavirus (HPV) type 16 (HPV16)-related squamous cell carcinoma of the head and neck (HNSCC).

Objectives: To evaluate the effectiveness of siRNA targeting E6 and/or E7 on the in vitro and in vivo growth suppression of HPV16-related HNSCC.

Methods: HPV16-related HNSCC (UM-SCC47) cell lines were used for the present study.

Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model.

Background: Although cancer therapy using replication-selective oncolytic adenoviruses has been available for many years, its anti-tumor efficacy is suboptimal as a result of low and nonspecific infectivity that depends on coxsackie adenovirus receptor expression of the target cancer and normal cells, and generation of an anti-adenovirus neutralizing antibody. In addition, concerns of triggering a severe innate immune response against the adenovirus limit the systemic administration. We developed the carrier cell-based oncolytic virus system (CBOVS) using irradiated tumor cells as carrier cells and concealing the adenovirus (Ad-IAI.

Immobilization of 293 cells using porous support particles for adenovirus vector production.

Adenovirus vector production by anchorage-independent 293 cells immobilized using porous biomass support particles (BSPs) was investigated in static and shake-flask cultures for efficient large-scale production of adenovirus vectors for gene therapy applications. The density of cells immobilized within BSPs was evaluated by measuring their WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) reduction activity. In shake-flask culture, 293-F cells, which were adapted to serum-free suspension culture, were not successfully retained within reticulated polyvinyl formal (PVF) resin BSPs (2 × 2 × 2 mm cubes) with matrices of relatively small pores (pore diameter 60 μm).

Adenovirus vector production using low-multiplicity infection of 293 cells.

The use of low-multiplicity infection of 293 cells in static culture with regular medium replacement was investigated for efficient large-scale production of adenovirus vectors for gene therapy applications. An adenovirus vector carrying the enhanced green fluorescent protein gene (Ad EGFP) was used to infect 293-F cells at a low multiplicity of infection (MOI) of 0.00001-0.