Transposon-based interferon gamma gene transfer overcomes limitations of episomal plasmid for immunogene therapy of glioblastoma

Despite improvements in gene delivery technology, transient expression of plasmid DNA has limited the efficacy of nonviral vectors applied to cancer gene therapy. We previously developed plasmid DNA vectors capable of transgene integration and long-term expression in human glioblastoma cells by util...

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Veröffentlicht in:	Cancer gene therapy 2007-06, Vol.14 (6), p.550-560
Hauptverfasser:	Wu, A, Oh, S, Ericson, K, Demorest, Z L, Vengco, I, Gharagozlou, S, Chen, W, Low, W C, Ohlfest, J R
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biomedical and Life Sciences Biomedicine Brain cancer Brain tumors Care and treatment Cell activation Cell Line Convection CpG islands Deoxyribonucleic acid DNA DNA Transposable Elements - genetics Enzyme-Linked Immunosorbent Assay Expression vectors Gene Expression Gene Therapy Gene transfer Genetic aspects Genetic Therapy - methods Genetic Vectors - genetics Glioblastoma Glioblastoma - immunology Glioblastoma - metabolism Glioblastoma - therapy Glioblastoma cells Glioblastoma multiforme Glioma Health aspects Humans Immunotherapy Integration Interferon gamma Interferon-gamma - genetics Interferon-gamma - immunology Lymphocytes T Methods Mice Mice, Inbred C57BL Oligonucleotides original-article Plasmids - genetics Polymerase chain reaction Reverse transcription Risk factors Transposase Transposases - genetics Transposases - metabolism Transposons Vectors (Biology) γ-Interferon
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Zusammenfassung:	Despite improvements in gene delivery technology, transient expression of plasmid DNA has limited the efficacy of nonviral vectors applied to cancer gene therapy. We previously developed plasmid DNA vectors capable of transgene integration and long-term expression in human glioblastoma cells by utilizing the Sleeping Beauty (SB) transposable element. In this study, we compared the efficacy of interferon gamma (IFN- γ ) immunogene therapy using episomal or SB vectors in a syngeneic GL261 glioma model. Gene delivery was achieved by intratumoral convection-enhanced delivery of DNA/polyethylenimine complexes. Only mice treated with SB transposase-encoding DNA to facilitate chromosomal integration exhibited a significant increase in survival ( P
ISSN:	0929-1903 1476-5500
DOI:	10.1038/sj.cgt.7701045