Adenovirus-mediated cancer gene therapy and virotherapy (Review)

Fukazawa,

doi:10.3892/ijmm_00000306

Cited by 40 publications

(51 citation statements)

References 60 publications

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“…27 For example, most adenoviruses cannot infect nondividing cells, such as cancer stem cells, which are a possible target of gene therapy. 28 Ideal carriers should possess the following characteristics: good targeted ability, no or low toxicity, easy detection and so on. Methods of delivering our therapeutic vectors into tumor masses will be the focus of our future research.…”

Section: Discussionmentioning

confidence: 99%

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

Ding

Zhang

et al. 2012

Cancer Gene Ther

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The AND gate functions such that when all inputs are activated the downstream gene will be transcribed and it is off otherwise. To accomplish optimal and targeted gene therapy in solid tumor patients, we have constructed an AND gate genetic circuit and investigated whether it could be activated by low-dose radiation in vitro and in vivo. The enhancement green fluorescent protein (EGFP) expression in different tumor cells transfected with control vector plxsn-EGFP confirmed that 2 Gy of radiation and 1% O 2 for 3 h could activate our AND gate. Besides, the obvious different levels of EGFP expression between 2 and 6 Gy of radiation demonstrated that the AND gate could be regulated by radiation doses. Additionally, through EGFP expression and the codistribution of p53 and HIF-1a in xenografts, we illustrated the targeted activation property of the AND gate and real-time monitoring to hypoxic districts in vivo. Moreover, significant growth inhibition and cell cycle arrest in vitro and apoptosis-inducing effects in vitro and in vivo proved that the AND gate induced ideal antitumor effects. In conclusion, the radiation dose-regulated AND gate genetic circuit could not only effectively monitor the therapeutic process in real-time but also induce ideal antitumor efficacy, and can be further exploited for personal therapy in clinical tumor patients.

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Section: Discussionmentioning

confidence: 99%

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

Ding

Zhang

et al. 2012

Cancer Gene Ther

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“…A pShuttle.IR.EGFP vector was created by removing Compared with other Ad vectors and single-vector recombination method, the systems presented here have the following features and advantages: First, they are based on the first generation Ad vectors deleted for E1 and E3, which have been widely investigated with respect to the bio-safety, molecular virology and host interaction. 22,23 Second, the specific tumor cell killing does not rely on E1 mutations that can compromise the production yield, viral replication and spread. 24,25 Third, in contrast to the tumorspecific promoters, the systems utilize a more universal strong CMV promoter to achieve high transgene expression.…”

Section: Construction Of Hravs and Ehravsmentioning

confidence: 99%

Homologous recombination-based adenovirus vector system for tumor cell-specific gene delivery

Lü

Liu

et al. 2013

Cancer Biology & Therapy

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“…However, they also possess significant advantages, such as efficient transgene delivery, expression in both dividing and non-dividing cells and ease of propagation to high titers (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…Although adenoviral vectors offer these advantages, poor tumor transduction efficiency in several types of tumor, dense stromal tissue impeding intratumoral virus spread and immunemediated viral clearance, remain the key factors limiting cancer gene therapy and virotherapy (1,4,5). Over a number of years, extensive research has been directed toward overcoming these limitations.…”

Section: Introductionmentioning

confidence: 99%

The effectiveness of the oncolytic activity induced by Ad5/F35 adenoviral vector is dependent on the cumulative cellular conditions of survival and autophagy

Kim

Kang

Song

et al. 2013

International Journal of Oncology

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Abstract.To overcome the poor tumor transduction efficiency of adenovirus serotype 5 (Ad5) observed in several types of cancer, the fiber region of Ad5, apart from its tail, was replaced by adenovirus serotype 35 (Ad35). The chimeric Ad5̸F35 adenoviral vector did not exhibit any significant enhancement of transduction efficiency. CD46, a receptor for Ad35, was expressed in relatively small amounts in most of the cancer cells examined. Therefore, we investigated the pivotal factor(s) that render cancer cells susceptible to transduction. We discovered that the tumor transduction efficiency of Ad5/F35 was enhanced in the presence of rapamycin, an autophagy inducer, in some cancer cells. Analysis of survival potential and cell proliferation rates revealed that Ad5/F35 exerted a more pronounced oncolytic effect in cancer cells with higher survival potential in the presence of rapamycin. IntroductionAdenoviral vectors are frequently used for gene transfer, in spite of their shortcomings, such as increased immunogenicity (which may occasionally prove beneficial in cancer treatment), prevalence of pre-existing anti-Ad immunity and lack of specific targeting. However, they also possess significant advantages, such as efficient transgene delivery, expression in both dividing and non-dividing cells and ease of propagation to high titers (1-3).Although adenoviral vectors offer these advantages, poor tumor transduction efficiency in several types of tumor, dense stromal tissue impeding intratumoral virus spread and immunemediated viral clearance, remain the key factors limiting cancer gene therapy and virotherapy (1,4,5). Over a number of years, extensive research has been directed toward overcoming these limitations. The reason for the poor transduction of adenoviral vectors is that tumor cells exhibit limited surface expression of the adenovirus 5 (Ad5) receptors, specifically the coxsackievirus and adenovirus receptor (CAR), α v β 3 and α v β 5 integrins. Therefore, numerous studies have focused on the modification of the adenoviral fiber region that binds to the receptors of tumor cells, to facilitate an eventual efficient infection. The structure of the fiber can be divided into three domains: an N-terminal tail, that attaches to the penton base, a central shaft with repeating motifs of ~15 residues and a C-terminal globular 'knob' domain, that functions as the cellular attachment site (6). The fiber knob has a central depression and three symmetry-related valleys, initially considered to be the binding sites for CAR (7). The first step involving the binding of the virus to the CAR receptor of target cells occurs via the C-terminal knob domain of the fiber protein. The second step is the interaction of Arg-Gly-Asp (RGD) motifs in the penton base with α v β 3 and α v β 5 integrins, which are the secondary host cell receptors, facilitating the internalization of virus via receptormediated endocytosis. However, Ad5-mediated gene transfer is inefficient in a number of tissues, such as endothelial (8,9), smooth muscle (8), d...

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Adenovirus-mediated cancer gene therapy and virotherapy (Review)

Cited by 40 publications

References 60 publications

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

Homologous recombination-based adenovirus vector system for tumor cell-specific gene delivery

The effectiveness of the oncolytic activity induced by Ad5/F35 adenoviral vector is dependent on the cumulative cellular conditions of survival and autophagy

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