Strategies for cancer gene therapy

Hughes, Rhiannon

doi:10.1002/jso.20001

Cited by 40 publications

(21 citation statements)

References 88 publications

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“…[10][11][12][13][14] By co-expression of TRAIL and a classical suicide gene, prodrug mediated apoptosis induction after outgrowth of the transduced cells would allow the efficient elimination of tumor cells. However, because the protein carryover in the viral particles caused by constitutive TRAIL expression in the packaging cells, this approach is impossible using the system described.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14] As attempts using prodrug-activating suicide genes or overexpression of tumor suppressor genes suffered from insufficient in vivo transduction rates, approaches leading to strong bystander killing of untransduced cells are important for successful cancer therapy. Recent studies describe TRAIL gene therapy approaches by using adenoviral or AAV vectors which have been found to suppress tumor growth in vivo using xenografted mice.…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

Wenger

Mattern²,

Haas

et al. 2006

Cancer Gene Ther

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, which selectively induces apoptosis in many transformed cells without apparent toxic side effects in normal tissue. We recently described the construction and characterization of a lentiviral vector for expression of TRAIL. In this report, we evaluate its suitability for therapeutic application. In vitro, we observed specific induction of apoptosis upon transduction in human lung cancer cells. Cell death was partially dependent on successful integration and TRAIL expression by the vectors, but was to some extent mediated by protein carryover, as we found TRAIL protein associated with virus particles. Transduction of subcutaneously growing lung tumors on nude mice with lentiviral TRAIL mediated a transient suppression of tumor growth. Analysis of tumor sections revealed that transduction efficiency of lentiviral control vector but not of lentiviral TRAIL vector was high. This was because of the direct cytotoxic activity of recombinant TRAIL present in viral particles, which prevented efficient tumor transduction. These data therefore suggest that enveloped viral vectors constitutively expressing TRAIL are well suited for ex vivo applications, such as the transduction of tumorhoming cells, but may have a lower effect when used directly for the transduction of tumor cells in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

Wenger

Mattern²,

Haas

et al. 2006

Cancer Gene Ther

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“…Recently, several strategies ONCOLOGY REPORTS 24: 897-907, 2010 897 High-level transgene expression mediated by the piggyBac transposon enhances transgenic therapeutic effects in cervical cancer xenografts have been investigated, such as oncogene inactivation, tumor suppressor gene replacement, inhibition of angiogenesis, drug sensitization (suicide genes), antisense strategies, and genetic immunotherapy (cytokines, co-stimulatory molecules, polynucleotide vaccination) (6). However, all in vitro and animal studies to date have not resulted in any clinical benefits.…”

Section: According To the Global Cancer Facts And Figures Published Bmentioning

confidence: 99%

High-level transgene expression mediated by the piggyBac transposon enhances transgenic therapeutic effects in cervical cancer xenografts

Kang

Yu²,

Sun³

et al. 2010

Oncol Rep

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Abstract.The piggyBac (PB) transposon is a recently identified, active and flexible transgene vector, combining the advantages of non-viral gene delivery with genomic integration and persistent transgene expression. In this study, we utilized the PB transposon to carry the herpes simplex thymidine kinase (HSV-tk) and red fluorescent protein (mRFP1) reporter genes into the HeLa cervical cancer cell line or tumor xenografts of cervical cancer. Our data showed that HSV-tk and mRFP1 were expressed in HeLa cells and tumor xenografts three weeks after intratumoral injection. The mRNA and protein levels of HSV-tk and mRFP1 were increased by using the PB transposon vector. Our system also demonstrated that sensitivity of transfected HeLa cells to the pro-drug ganciclovir (GCV) was enhanced in vitro and in vivo. Furthermore, our data indicated that the enhanced transgenic therapeutic effect was strongly associated with high-level transgene expression mediated by the PB transposon. Our results suggest that applying the PB transposon in HSV-tk gene delivery and GCV treatment is a promising gene therapy strategy in the treatment of cervical cancer.

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“…Among these strategies, transfection of tumor suppression genes into cancer cells has been considered as a promising tool for arresting cell growth and inducing apoptosis. 5 To date, studies report that a variety of tumor suppression genes, such as p53, 6,7 Rb, 8 and PTEN, 9 have been successfully applied in cancer gene therapy.…”

Section: Introductionmentioning

confidence: 99%

Suppression of tumor growth in xenograft model mice by programmed cell death 4 gene delivery using folate-PEG-baculovirus

Kwon

Choi

et al. 2010

Cancer Gene Ther

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Strategies for cancer gene therapy

Cited by 40 publications

References 88 publications

Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

High-level transgene expression mediated by the piggyBac transposon enhances transgenic therapeutic effects in cervical cancer xenografts

Suppression of tumor growth in xenograft model mice by programmed cell death 4 gene delivery using folate-PEG-baculovirus

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