Cancer gene therapy using in vivo electroporation of Flt3-ligand

Shimao, Kazuya; Takayama, Takuya; Enomoto, Katsuhisa; Saito, Tetsuya; Nagai, Shigenori; Miyazaki, Junichi; Ogawa, Kenji; Tahara, Hideaki

doi:10.3892/ijo.27.2.457

Cited by 7 publications

(11 citation statements)

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“…In conclusion, we found that intramuscular plasmidbased codelivery of GM-CSF and FLT3-L cDNA is an effective, simple and inexpensive method for generating DCs. Recently, Shimao et al [Shimao, K. et al, 2005] have reported results similar to ours in the application of FLT3-L gene therapy. This method simplifies the usual in vivo DC expansion protocols, which rely on purified protein injections and could find many applications in immunotherapeutic studies.…”

Section: Generation Of Dcs By Administration Of Plasmids Encoding Gm-supporting

confidence: 78%

Electroporation-Enhanced Nonviral Gene Transfer for the Prevention or Treatment of Immunological, Endocrine and Neoplastic Diseases

Prud’homme

Glinka²,

Khan³

et al. 2006

CGT

168

118

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Nonviral gene transfer is markedly enhanced by the application of in vivo electroporation (also denoted electro-gene transfer or electrokinetic enhancement). This approach is safe and can be used to deliver nucleic acid fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues, such as skeletal muscle, skin and liver. In this review, we address the principles of electroporation and demonstrate its effectiveness in disease models. Electroporation has been shown to be equally applicable to small and large animals (rodents, dogs, pigs, other farm animals and primates), and this addresses one of the major problems in gene therapy, that of scalability to humans. Gene transfer can be optimized and tissue injury minimized by the selection of appropriate electrical parameters. We and others have applied this approach in preclinical autoimmune and/or inflammatory diseases to deliver either cytokines, anti-inflammatory agents or immunoregulatory molecules. Electroporation is also effective for the intratumoral delivery of therapeutic vectors. It strongly boost DNA vaccination against infectious agents (e.g., hepatitis B virus, human immunodeficiency virus-1) or tumor antigens (e.g., HER-2/neu, carcinoembryonic antigen). In addition, we found that electroporation-enhanced DNA vaccination against islet-cell antigens ameliorated autoimmune diabetes. One of the most likely future applications, however, may be in intramuscular gene transfer for systemic delivery of either endocrine hormones (e.g., growth hormone releasing hormone and leptin), hematopoietic factors (e.g., erythropoietin, GM-CSF), antibodies, enzymes, or numerous other protein drugs. In vivo electroporation has been performed in humans, and it seems likely it could be applied clinically for nonviral gene therapy.

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Section: Generation Of Dcs By Administration Of Plasmids Encoding Gm-supporting

confidence: 78%

Electroporation-Enhanced Nonviral Gene Transfer for the Prevention or Treatment of Immunological, Endocrine and Neoplastic Diseases

Prud’homme

Glinka²,

Khan³

et al. 2006

CGT

168

118

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“…To study in vivo effects associated with systemic administration of IL-23, we used IVE into the bilateral pretibial muscles, which allows the prolonged production and release to systemic blood circulation of large amount of proteins (30). To confirm the transgene expression of IVE, the plasmids were transfected into the pretibial muscles of mice, and the expression of each subunit was examined using RT-PCR.…”

Section: Systemic Administration Of Il-23 Protein At High Levels Was mentioning

confidence: 99%

“…Each experimental group consisted of five to eight animals. On day 9, when tumor size reached ϳ6 -8 mm 2 , IVE was performed as described below (30). Briefly, mice were anesthetized with pentobarbital sodium and injected with plasmid DNA diluted in sterile saline (50 l, 1 g/l) into the bilateral pretibial muscles using a tuberculin syringe with 27-gauge needles.…”

Section: Animal Experiments Using Ivementioning

confidence: 99%

Systemic Administration of IL-23 Induces Potent Antitumor Immunity Primarily Mediated through Th1-Type Response in Association with the Endogenously Expressed IL-12

Kaiga

Sato

Kaneda

et al. 2007

The Journal of Immunology

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IL-23, a cytokine, which is composed of the p40 subunit shared with IL-12 and the IL-23-specific p19 subunit, has been shown to preferentially act on Th1 effector/memory CD4+ T cells and to induce their proliferation and IFN-γ production. The IL-23 is also reported to act on Th17-CD4+ T cells, which are involved in inducing tissue injury. In this study, we examined the antitumor effects associated with systemic administration of IL-23 and their mechanisms in mouse tumor system. Systemic administration of high-dose IL-23 was achieved using in vivo electroporation of IL-23 plasmid DNA into the pretibial muscles of C57BL/6 mice. The IL-23 treatment was associated with significant suppression of the growth of pre-existing MCA205 fibrosarcoma and prolongation of the survival of treated mice without significant toxicity when compared with those of the mice treated with EGFP. Although the therapeutic outcomes were similar to those with the IL-12 treatment, the IL-23 treatment induced characteristic immune responses distinctive to those of IL-12 treatment. The IL-23 administration even at the therapeutic levels did not induce detectable IFN-γ concentration in the serum. In vivo depletion of CD4+ T cells, CD8+ T cells, or NK cells significantly inhibited the antitumor effects of IL-23. Furthermore, the CD4+ T cells in the lymph nodes in the IL-23-treated mice showed significant IFN-γ and IL-17 response upon anti-CD3 mAb stimulation in vitro. These results and the ones in the IFN-γ or IL-12 gene knockout mice suggest that potent antitumor effects of IL-23 treatment could be achieved when the Th1-type response is fully promoted in the presence of endogenously expressed IL-12.

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“…6 It has been used in the laboratory for gene delivery to cells in vitro or in vivo, and is recently receiving much attention in cancer gene therapy as a clinically applicable method for enhancing gene delivery, based on it being carried out safely and easily with low cost. [7][8][9] In this method, plasmid DNA is injected into target tissue after which a series of electric pulses that induce temporary and reversible breakdown of cell membrane and pore formation is conducted to augment DNA transport into the cells. It has been applied to not only accessible surface tissue but also to deep tissues.…”

Section: Introductionmentioning

confidence: 99%

Visualization of in vivo electroporation-mediated transgene expression in experimental tumors by optical and magnetic resonance imaging

Aung¹,

Hasegawa²,

Koshikawa-Yano³

et al. 2009

Gene Ther

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In vivo electroporation (EP) is an efficient method for effective gene transfer and is highly expected for application in anticancer gene therapy. Non-invasive monitoring of gene transfer/expression is critical for optimal gene therapy. Here we report in vivo optical and high-field magnetic resonance imaging (MRI) of EP-mediated transgene expression in a tumor model. Initially, we observed spatio-temporal change in in vivo EP-mediated transgene expression by optical imaging using red fluorescence protein (RFP) as a reporter gene. Next, we constructed a dual-reporter plasmid carrying a gene-encoding MRI reporter ferritin heavy chain and RFP gene to visualize the intratumoral transgene expression by dual modality. Cells transfected with this plasmid showed lower signal intensity on in vitro T 2 -weighted cellular MRI and quantitatively increased the transverse relaxation rate (1/T 2 ) compared with control cells. After conducting in vivo EP in an experimental tumor, the plasmidinjected region showed both fluorescent emissions in optical imaging and detectably lowered signal on T 2 -weighted MRI. The correlative immunohistological findings confirmed that both the reporter transgenes were co-expressed in this region. Thus, our strategy provides a platform for evaluating EP-mediated cancer gene therapy easily and safely without administering contrast agent or substrate.

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Cancer gene therapy using in vivo electroporation of Flt3-ligand

Cited by 7 publications

References 0 publications

Electroporation-Enhanced Nonviral Gene Transfer for the Prevention or Treatment of Immunological, Endocrine and Neoplastic Diseases

Electroporation-Enhanced Nonviral Gene Transfer for the Prevention or Treatment of Immunological, Endocrine and Neoplastic Diseases

Systemic Administration of IL-23 Induces Potent Antitumor Immunity Primarily Mediated through Th1-Type Response in Association with the Endogenously Expressed IL-12

Visualization of in vivo electroporation-mediated transgene expression in experimental tumors by optical and magnetic resonance imaging

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