Genetic strategies for brain tumor therapy

Lawler, Sean E.; Peruzzi, Pierpaolo; Chiocca, E. Antonio

doi:10.1038/sj.cgt.7700886

Cited by 54 publications

(37 citation statements)

References 85 publications

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“…These therapeutic strategies have been translated into clinical trials. 3,4 Unfortunately, to date, the results achieved from most clinical trials have not shown substantial therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas

et al. 2007

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The targeted expression of transgenes is one of the principal goals of gene therapy, and it is particularly relevant for the treatment of brain tumors. In this study, we examined the effect of the overexpression of human gas1 (growth arrest specific 1) and human p53 cDNAs, both under the transcriptional control of a promoter of the human glial fibrillary acidic protein (gfa2), employing adenoviral expression vectors, in glioma cells. We showed that the targeted overexpression of gas1 and p53 (AdSGas1 and AdSp53, respectively) in rat glioma cells (C6) reduced the number of viable cells and induced apoptosis. Moreover, the adenovirally targeted expression of these genes also reduced tumor growth in vivo. Unexpectedly, there was no additive effect when both gas1 and p53 were simultaneously expressed in the same cells using a bicistronic adenoviral vector. We suggest that Gas1 does not act in combination with p53 in the C6 and U373 glioma cell lines, inducing apoptosis and cell cycle arrest. Our results indicate that the targeted expression of tumor suppressor genes (gas1 and p53) regulated by the gfa2 promoter, together with adenoviral vectors may provide an interesting approach for adjuvant selective glioma gene therapy.

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Section: Introductionmentioning

confidence: 99%

Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas

et al. 2007

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“…Recent studies suggest that stem cells can be used as vehicles for delivering therapeutic genes to treat brain tumors (3)(4)(5). Neural stem cells exhibit extensive tropism for experimental gliomas and migrate toward outgrowing microsatellites (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Gene Therapy Using TRAIL-Secreting Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells against Intracranial Glioma

Kim¹,

Lim²,

Park³

et al. 2008

Cancer Research

261

229

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Adenovirus-mediated gene therapies against brain tumors have been limited by the difficulty in tracking glioma cells infiltrating the brain parenchyma. Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSC) are particularly attractive cells for clinical use in cell-based therapies. In the present study, we evaluated the tumor targeting properties and antitumor effects of UCB-MSCs as gene delivery vehicles for glioma therapy. We efficiently engineered UCB-MSCs to deliver a secretable trimeric form of tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) via adenoviral transduction mediated by cellpermeable peptides. We then confirmed the migratory capacity of engineered UCB-MSCs toward tumor cells by an in vitro migration assay and by in vivo injection of UCB-MSCs into the tumor mass or the opposite hemisphere of established human glioma in nude mice. Moreover, in vitro coculture, experiments on Transwell plates, and in vivo survival experiments showed that MSC-based stTRAIL gene delivery has more therapeutic efficacy compared with direct injection of adenovirus encoding the stTRAIL gene into a tumor mass. In vivo efficacy experiments showed that intratumoral injection of engineered UCB-MSCs (MSCs-stTRAIL) significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with controls. These results suggest that human UCB-MSCs have potential use as effective delivery vehicles for therapeutic genes in the treatment of intracranial glioma. [Cancer Res 2008;68(23):9614-23]

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“…The strategies of gene therapy can be categorized as follows (Mut& Ziyal,2010 Immune gene therapy aims to enhance the T cell mediated immune responce againts to brain neoplasms by using genetically modified T cell therapy, vaccination therapy and cytokine therapy (Iwami et al, 2010). Cytotoxic therapy is mainly consist of either delivering of gene or virus therapy (Aboody et al, 2008;Aghi & Chiocca, 2006;Candolfi et al, 2009;Kroeger et al, 2010;Lawler et al, 2006). The most common studied conditional cytotoxic transgene is Herpes Simplex Type 1 thymidine kinase (TK), which converts the prodrug ganciclovir (or valacyclovir) into the highly toxic deoxyguanosine triphosphate causing early chain termination of nascent DNA strands (Beltinger et al, 1999).…”

Section: Genetic and Immunology Of Brain Tumorsmentioning

confidence: 99%