Human Gene Therapy for Malignant Gliomas (Glioblastoma Multiforme and Anaplastic Astrocytoma) by <i>In Vivo</i> Transduction with Human Interferon <i>β</i> Gene Using Cationic Liposomes

Yoshida, Jun; Mizuno, Masaaki; Fujii, Masazumi; Kajita, Yasukazu; Nakahara, Norimoto; Hatano, Manabu; Saito, Ryuta; Nobayashi, Misato; Wakabayashi, Toshihiko

doi:10.1089/10430340460732472

Cited by 125 publications

(70 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[13][14][15][16] On the basis of these observations, a phase I clinical trial of IFN-b gene therapy was performed on five patients with recurrent malignant glioma. 9 At 10 weeks after treatment initiation, two patients showed more than 50% tumor reduction, whereas others did not show any significant improvement. The median survival was longer in the treated subjects than in the matched historical controls from our institution.…”

Section: F3cdifn-b Cells Increase the Survival Periods In Experimenmentioning

confidence: 89%

“…3 An expression plasmid was constructed using the pBabePuro retroviral vector (Cell Biolabs, San Diego, CA) as the backbone to include the human IFN-b cDNA transcribed from the long terminal repeat ends of the IFN-b gene. 9,10 The IFN-b.puro plasmid and the MV12 envelope-coding plasmid (provided by Dr KS Aboody 3 ) were cotransduced into pA317 cells (ATCC). The supernatant containing the IFN-b-expressing retroviral vector was used for multiple infections of the F3.CD cells.…”

Section: Human Glioma Cells and Nscsmentioning

confidence: 99%

“…In our pilot clinical trial, liposome-mediated IFN-b gene therapy has shown potent antitumor activity in patients with malignant glioma. 9,10 The clinical trial suggested that the IFN-b gene delivery permitted locally sustained IFN-b production at levels sufficient to yield antitumor efficacy with minimal systemic adverse effects.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human neural stem cells transduced with IFN-β and cytosine deaminase genes intensify bystander effect in experimental glioma

et al. 2009

View full text Add to dashboard Cite

Previously, we have shown that the genetically modified human neural stem cells (NSCs) show remarkable migratory and tumortropic capability to track down brain tumor cells and deliver therapeutic agents with significant therapeutic benefit. Human NSCs that were retrovirally transduced with cytosine deaminase (CD) gene showed remarkable 'bystander killer effect' on the glioma cells after application of the prodrug, 5-fluorocytosine (5-FC). Interferon-b (IFN-b) is known for its antiproliferative effects in a variety of cancers. In our pilot clinical trial in glioma, the IFN-b gene has shown potent antitumor activity in patients with malignant glioma. In the present study, we sought to examine whether human NSCs genetically modified to express both CD and IFN-b genes intensified antitumor effect on experimental glioma. In vitro studies showed that CD/IFN-b-expressing NSCs exerted a remarkable bystander effect on human glioma cells after the application of 5-FC, as compared with parental NSCs and CD-expressing NSCs. In animal models with human glioma orthotopic xenograft, intravenously infused CD/IFN-b-expressing NSCs produced striking antitumor effect after administration of the prodrug 5-FC. Furthermore, the same gene therapy regimen prolonged survival periods significantly in the experimental animals. The results of the present study indicate that the multimodal NSC-based treatment strategy might have therapeutic potential against gliomas.

show abstract

Section: F3cdifn-b Cells Increase the Survival Periods In Experimenmentioning

confidence: 89%

Section: Human Glioma Cells and Nscsmentioning

confidence: 99%

See 1 more Smart Citation

Human neural stem cells transduced with IFN-β and cytosine deaminase genes intensify bystander effect in experimental glioma

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This approach has already been used as a promising tool for brain protection and repair from neuronal insults and degeneration, not only in several animal models 3,4,12,29,52,53 but also in some clinical trials. 54,55 The use of cationic liposomes as gene delivery systems has proven to be a less toxic and immunogenic approach as compared to the use of viral vectors, thus representing a viable alternative to the extensively employed viral vectors.…”

Section: Discussionmentioning

confidence: 99%

Tf-lipoplex-mediated NGF gene transfer to the CNS: neuronal protection and recovery in an excitotoxic model of brain injury

et al. 2005

View full text Add to dashboard Cite

The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present evidence of the successful delivery and expression of both a reporter and a therapeutic gene in the rodent brain, as evaluated by immunohistochemical assays. Our results indicate that transferrin-associated cationic liposome/DNA complexes (Tf-lipoplexes) allow a significant enhancement of transfection activity as compared to plain complexes, and that 8/1 (+/À) Tf-lipoplexes constitute the best formulation to mediate in vivo gene transfer. We demonstrated that Tf-lipoplex-mediated nerve growth factor transgene expression attenuates the morphological damages of the kainic acid-induced lesion as assessed by 2,3,5-triphenyltetrazolium chloride (TTC) vital staining. These findings suggest the usefulness of these lipid-based vectors in mediating the delivery of therapeutic genes to the CNS.

show abstract

“…Nonetheless, cationic liposomes have been used to deliver therapeutic genes in a human brain tumor trial. 21 Successful gene delivery using immunoliposomes specifically targeted to glioma cells with monoclonal antibodies has been reported. 22 Finally, there are occasional examples of the use of naked plasmid DNA in brain tumor gene therapy.…”

Section: Advances In Gene Delivery Methodsmentioning

confidence: 99%

Genetic strategies for brain tumor therapy

2005

View full text Add to dashboard Cite

Gene therapy is a potentially useful approach in the treatment of human brain tumors, which are notoriously refractory to conventional approaches. Most human clinical trials to date have been unsuccessful in terms of improving patient outcome. Recent improvements in viral vectors, the development of stem cell technology, and increased understanding of the mechanism of action of therapeutic transgenes provide hope that the next generation of gene therapeutics may show increased efficacy in treatment of this devastating disease.

show abstract

Human Gene Therapy for Malignant Gliomas (Glioblastoma Multiforme and Anaplastic Astrocytoma) by In Vivo Transduction with Human Interferon β Gene Using Cationic Liposomes

Cited by 125 publications

References 21 publications

Human neural stem cells transduced with IFN-β and cytosine deaminase genes intensify bystander effect in experimental glioma

Human neural stem cells transduced with IFN-β and cytosine deaminase genes intensify bystander effect in experimental glioma

Tf-lipoplex-mediated NGF gene transfer to the CNS: neuronal protection and recovery in an excitotoxic model of brain injury

Genetic strategies for brain tumor therapy

Contact Info

Product

Resources

About