A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis

Guan, Jun; Jiang, An; Qian, Cheng; Tian, Hui; Li, Liantao; Zheng, Junnian

doi:10.1007/s13277-013-0701-7

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…Compared with the hTERT and survivin promoters, the Ki67 core promoter possesses greater transcription activity and more desirable tumour selectivity (Pei et al , 2012). In addition, our laboratory has demonstrated that Ki67-ZD55-IL-24 could improve the anti-tumour effects of the alkylating agent temozolomide in melanoma cells (Jiang et al , 2013). …”

Section: Discussionmentioning

confidence: 99%

“…The recombinant adenoviruses used in this study have been previously described (Zhao et al , 2005; Jiang et al , 2013), which included Ki67 promoter-controlled ZD55 carrying IL-24 (Ki67-ZD55-IL-24), Ki67 promoter-controlled ZD55 (Ki67-ZD55), ZD55 carrying IL-24 (ZD55-IL-24), and ZD55 carrying enhanced green fluorescence protein (ZD55-EGFP). The Ki67 promoter used in this study was constructed previously (Wang et al , 2011; Pei et al , 2012).…”

Section: Methodsmentioning

confidence: 99%

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Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion

Jiang

et al. 2014

Br J Cancer

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Background:Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells.Methods:Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT–PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay.Results:Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice.Conclusions:This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion

Jiang

et al. 2014

Br J Cancer

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“…In addition, IL-24 is a good candidate for sensitizing tumor cells to radiotherapy without exacerbating toxicity, due to tumor-specific anti-angiogenic, pro-apoptotic and growth-inhibitory activities (17)(18)(19). A novel oncolytic adenovirus with E1A gene controlled by Ki67 promoter has been constructed, expressing the IL-24 gene (10). The Ki67 promoter is a potent controlling element of E1A.…”

Section: Discussionmentioning

confidence: 99%

“…The cells were screened routinely to verify the lack of mycoplasma contamination for use in the long phase of growth. The recombinant adenoviruses used in the present study, including Ki67 promoter-controlled ZD55 carrying IL-24 (Ki67-ZD55-IL-24), Ki67 promoter-controlled ZD55 (Ki67-ZD55) and ZD55 carrying IL-24 (ZD55-IL-24), have been previously described (8,10). The Ki67 promoter used in the present study was previously constructed (11).…”

Section: Introductionmentioning

confidence: 99%

Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death

Chen

et al. 2014

Molecular Medicine Reports

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Abstract. Renal cell carcinoma is the most frequent kidney malignancy and patients with metastatic disease have a poor prognosis. Suppressed apoptosis and marked invasiveness are distinctive features of renal cell carcinoma. In the present study, a dual-regulated oncolytic adenovirus expressing the interluekin (IL)-24 gene (Ki67-ZD55-IL-24) was constructed utilizing the Ki67 promoter to replace the native viral promoter of the E1A gene. Whether the combination of Ki67-ZD55-IL-24-mediated gene virotherapy and radiotherapy produced increased cytotoxicity in renal cell carcinoma cells via mitochondrial apoptotic cell death was investigated. The data indicated that this novel strategy has the potential to be further developed into an effective approach to treat renal cell carcinoma. The results showed that the combination of Ki67-ZD55-IL-24 and radiotherapy significantly enhanced anti-tumour activity via increasing the induction of apoptosis in melanoma cells compared with the other agents. IntroductionRenal cell carcinoma (RCC) is the most frequent kidney malignancy and patients with metastatic RCC have a poor prognosis (1). In the United States, RCC is diagnosed in ~51,000 patients each year (2). If the disease is detected at an early stage, a large portion of the kidney or the entire organ may be removed, and prolonged patient survival may be achieved (3). However, if the disease has spread beyond the capsule of the kidney into the adrenal gland or surrounding fascia with nodal involvement, the prognosis is poor with rapid progression. In addition, RCC is frequently characterized as highly refractory to multiple established cytotoxic radiotherapy and chemotherapy regimens.Previous data have suggested that interleukin 24 (IL-24) is a promising candidate for cancer gene therapy (4). IL-24 has been demonstrated to suppress growth and induce apoptosis in a wide range of human cancer types without apparent cytotoxicity to normal cells (4). Recent studies have shown that IL-24 radiosensitizes various cancer cells, including non-small cell lung carcinoma, renal carcinoma and malignant glioma cells (5).Ki-67 is an established proliferation mediator and is used extensively to estimate the proliferation fraction of tumors (6). The Ki67 labeling index is an independent predictor of disease progression and recurrence in carcinomas, and also is used as a grade index and prognostic marker. The Ki-67 gene promoter is a tumor-selective promoter with the desired specificity and efficiency to further restrict transgene expression in tumor cells and improve the targeting of gene therapy (7).Oncolytic adenoviruses are a novel class of therapeutic agent in cancer treatment. A previous study observed that the E1B 55-kDa gene-defective oncolytic adenovirus ZD55 not only efficiently infected, replicated in and lysed tumor cells, but also amplified IL-24 gene expression levels. Furthermore, the increased expression levels of IL-24 in the tumor microenvironment did not affect adjacent normal cells (8).One strategy to achieve the desired t...

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“…Moreover, the clinical activity of oncolytic viruses seems to benefit from some extent of initial immunosuppression (which facilitates viral spread, see below) followed by the administration of immunostimulatory molecules (which exacerbate antitumor immunity) 1 , 5 . In line with this notion, oncolytic viruses have also been engineered to express (1) tumor-associated antigens (generating so-called oncolytic vaccines); 75 - 79 (2) co-stimulatory molecules, such as CD40 ligand (CD40L) and CD80; 80 - 84 (3) immunostimulatory cytokines, including interleukin (IL)-2, 85 - 87 IL-12, 88 - 95 IL-15, 96 - 101 IL-23, 102 IL-24, 103 - 106 and granulocyte macrophage colony-stimulating factor (GM-CSF); 73 , 89 , 107 - 113 or (4) chemokines, such as chemokine (C-C motif) ligand 7 (CCL7) 114 and CCL19 115 …”

Section: Introductionmentioning

confidence: 99%

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et al. 2014

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Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of oncolytic virotherapy in oncological indications.

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A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis

Cited by 14 publications

References 23 publications

Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion

Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion

Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death

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