Viral-based gene delivery and regulated gene expression for targeted cancer therapy

Lü, Yi; Madu, Chikezie O.

doi:10.1517/17425240903419608

Cited by 24 publications

(14 citation statements)

References 121 publications

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“…In addition to bacterial treatment, biological therapy with viruses is also being studied by modern research. ( 51,52 ) To discriminate between cancer cells and non‐cancerous cells, genetically engineered oncolytic viruses have been constructed to target tumors by exploiting each cancer’s unique biology. The efficacy can be enhanced by carrying therapeutic genes to induce cellular apoptosis/suicide and/or facilitate tumor/virus imaging.…”

Section: Bacterial Therapy For Cancermentioning

confidence: 99%

“…Some viruses are armed with genes to affect the tumor microenvironment, such as genes encoding for angiostatic factors, inflammatory cytokines, or proteases that modulate the extracellular matrix to suppress tumor vascularization, or to enhance antitumor immune responses and viral spread throughout the solid tumor. ( 51,52 )…”

Section: Bacterial Therapy For Cancermentioning

confidence: 99%

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Targeting solid tumors with non‐pathogenic obligate anaerobic bacteria

Taniguchi

Fujimori

Sasaki³

et al. 2010

Cancer Science

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Molecular‐targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non‐pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. (Cancer Sci 2010)

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Section: Bacterial Therapy For Cancermentioning

confidence: 99%

Section: Bacterial Therapy For Cancermentioning

confidence: 99%

Targeting solid tumors with non‐pathogenic obligate anaerobic bacteria

Taniguchi

Fujimori

Sasaki³

et al. 2010

Cancer Science

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show abstract

“…Although inducible promoters offer the potential to selectively control therapeutic gene expression in the tumor with little normal tissue toxicity; however, when activated, these promoters often result in lower activity, and transgene expres-sion is limited to the period of stimulation and returns to basal levels following withdrawal of the induction trigger. (26,27) In our experiments, continuous growth inhibition of xenografts with active AND gate genetic circuit demonstrated that after activation, the AND gate vectors could make persistent antitumor effects in vivo and might overcome the temporary expression from inducible promoter.…”

Section: Discussionmentioning

confidence: 80%

p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy

Ding

Wang³

et al. 2015

Cancer Science

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Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6, heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non-small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation- and hypoxia-activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side-effects of clinical radiation therapy.

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“…In recent years, numerous classes of tumour-targeting agents have been developed including small molecules [40], antibodies [41][42][43], nanoparticles [44,45], viral [46][47][48] and non-viral gene vectors [49][50][51], and cell-based vectors [4- 19,[27][28][29][30][31][32]. Traditionally, the development of cellbased therapies has focused on the use of stem-cells including tissue-specific stem cells, pluripotent stem cells or mesenchymal stem cells [5,6,[8][9][10][11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Engineering “self-homing” circulating tumour cells as novel cancer theranostics

Parkins

Dubois

Kelly³

et al. 2019

Preprint

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Purpose: New ways to target and treat metastatic disease are urgently needed. Tumor "selfhoming" describes the recruitment of circulating tumor cells (CTCs) back to a previously excised primary tumor location, contributing to tumor recurrence, as well as their migration to established metastatic lesions. Recently, self-homing CTCs have been exploited as delivery vehicles for anti-cancer therapeutics in preclinical primary tumor models. However, the ability of CTCs to self-home and treat metastatic disease is largely unknown. Methods: Here, we employ molecular imaging to explore whether systemically-administered CTCs home to metastatic lesions and if CTCs armed with both a reporter gene and a cytotoxic prodrug gene therapy can be used to visualize and treat metastatic disease. Results: Bioluminescence imaging (BLI) performed over time revealed a remarkable ability of CTCs to home to primary and metastatic tumors throughout the body. Mice that received therapeutic CTCs had less BLI signal as well as less primary tumour burden than control mice. Preliminary data also showed self-homing therapeutic CTCs may be effective at treating disseminated breast cancer metastases.Conclusion: Using dual-luciferase BLI, this study demonstrates the noteworthy ability of experimental CTCs to home to disseminated breast cancer lesions. Moreover, by incorporating a prodrug gene therapy system into our self-homing CTCs, we show exciting progress towards effective and targeted delivery of gene-based therapeutics to treat both primary and metastatic lesions.

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Viral-based gene delivery and regulated gene expression for targeted cancer therapy

Abstract: A summary of existing challenges and future directions is also included.

Cited by 24 publications

References 121 publications

Targeting solid tumors with non‐pathogenic obligate anaerobic bacteria

Targeting solid tumors with non‐pathogenic obligate anaerobic bacteria

p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy

Engineering “self-homing” circulating tumour cells as novel cancer theranostics

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