Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter.

Chen, Ling; Chen, Dongshu; Manome, Yoshinobu; Dong, Yaa Hui; Fine, Howard A.; Küfe, Donald

doi:10.1172/jci118347

Cited by 104 publications

(48 citation statements)

References 29 publications

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“…[1][2][3] These include the tyrosinase promoter for directing gene expression to melanoma cells, [4][5][6] the ␣-fetoprotein promoter for hepatoma cells, 7 the mucin-1 promoter for mammary carcinoma, 8 the prostate-specific antigen promoter for prostate carcinoma 9 or the neuron-specific enolase promoter for neuronal cells. 10 In other studies, transcriptional control elements which can stimulate transcription in response to disease-specific alterations, such as hypoxic conditions 11 or the loss of cell cycle checkpoints in tumors, 12 have also been used.…”

Section: Introductionmentioning

confidence: 99%

A strategy for enhancing the transcriptional activity of weak cell type-specific promoters

1998

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Cell type-and tissue-specific promoters play an important moter to drive the simultaneous expression of the desired role in the development of site-selective vectors for gene effector/reporter gene product and a strong artificial trantherapy. A large number of highly specific promoters has scriptional activator which stimulates transcription through been described, but their applicability is often hampered appropriate binding sites in the promoter. Using a VP16-by their inefficient transcriptional activity. In this study, weLexA chimeric transcription factor, we show that this describe a new strategy for enhancing the activity of weak approach leads to a 14-to Ͼ100-fold enhancement of both promoters without loss of specificity. The basic principle of the endothelial cell-specific von Willebrand factor promoter this strategy is to establish a positive feedback loop which and the gastrointestinal-specific sucrase-isomaltase prois initiated by transcription from a cell type-specific promoter while maintaining approximately 30-to Ͼ100-fold moter. This was achieved by using a cell type-specific procell type specificity.

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Section: Introductionmentioning

confidence: 99%

A strategy for enhancing the transcriptional activity of weak cell type-specific promoters

1998

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“…Control of gene expression through tissue promoters has been widely used for targeting the transgene expression, which includes the tyrosinase gene promoter in melanomas, the carcinoembryonic antigen promoter in colorectal cancers, the E2F promoter in cancers that carry a defective retinoblastoma gene and MUC 1 promoter in breast cancers. [45][46][47][48] However, most of these promoters are relatively weaker than other commonly used viral promoters such as cytomegalovirus and SV40 early promoters. Therefore, the use of these tissue-specific promoters has been hampered by the problem of low expression.…”

Section: Discussionmentioning

confidence: 99%

Transgene expression of α tumor necrosis factor with mutations D142N and A144R under control of human telomerase reverse transcriptase promoter eradicates well-established tumors and induces long-term antitumor immunity

2008

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Recombinant adenoviral vectors (AdVTNF-a) expressing a tumor necrosis factor (TNF-a) under control of cytomegalovirus (CMV) promoter have been used in cancer gene therapy. To reduce its cytotoxicity, we constructed a recombinant AdV TERT mTNF-a expressing a mutant TNF-a (mTNF-a) with mutations at D142N and A144R under control of human telomerase reverse transcriptase (hTERT) promoter for treatment of well-established ovalbumin (OVA)-expressing murine B16 melanoma (BL6-10 OVA ) (6 mm in diameter). We demonstrated that the mTNF-a with mutations at D142N and A144R has less in vitro cytotoxicity, but maintains its functional effect in the stimulation of T-cell proliferation. The in vitro and in vivo transgene expressions under control of hTERT promoter are highly restricted in tumor cells compared with those under the control of the CMV promoter. AdV TERT mTNF-a gene therapy by intratumoral injection of AdV TERT mTNF-a vector (2 Â 10 9 PFU) expressing the mutant mTNF-a under control of hTERT promoter reduces its in vivo toxicity, eradicates well-established BL6-10 OVA tumors in 4/10 tumor-bearing mice, and induces OVAspecific CD8 þ T-cell-mediated long-term antitumor immunity. Therefore, AdV TERT mTNF-a gene therapy may be very useful in the immunotherapy of cancer.

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“…13 Effectiveness of this strategy was further refined by incorporation of a breast cancer specific promoter. 9,11 In an effort to develop a suitable strategy to purge leukemia cells from HPC, we proposed to develop an MCV, which would be capable of effectively transducing both leukemia cells and primary HPC. 12 On the other side, such a tropism independent vector may also deliver equal toxicity to both normal and leukemia cells, thus killing HPC at similar efficacy as it would kill malignant cells abating a potential therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies utilizing gene transfer for purging of human stem cells have successfully used adenovirus to eliminate breast cancer cells. [9][10][11] Breast cancer cells are permissive to adenovirus infection while hematopoietic cells are not, because hematopoietic cells do not express or only minimally express the coxsackie adenovirus receptor (CAR). 10,12,13 Therefore, although previously reported adenovirus-purging strategies are viable for CAR positive cancers, they would not be successful for the purging of leukemia cells.…”

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confidence: 99%

Development of a gene therapy based bone marrow purging system for leukemias

et al. 2005

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Although viable gene therapy based methods have been reported for the selective removal or purging of contaminating epithelial derived cancer cells from stem cell grafts, similar strategies for the purging of leukemia cells have been significantly less efficient. Hematopoietic cells are difficult targets for transduction with currently available vectors. Polylysine based molecular conjugate vectors (MCV) were previously found to effectively transduce both normal and malignant hematopoietic cells. A panel of human leukemia cell lines as well as CD34 þ selected primary human hematopoietic progenitor cells (HPC) were tested for differential gene expression utilizing different promoters. Reporter gene expression under the control of RSV and SV40 promoters showed a 6-log fold increase in leukemia cells when compared to primary HPC. Using a polylysine based recombinant molecular conglomerate vector (recMCV) encoding the HSV-tk suicide gene under control of RSV, we demonstrated effective and specific cell killing in all leukemia cell lines as well as in primary human leukemia cells derived from chemotherapy refractory patients, while HPC survived under the same conditions at approximately 20% viability. These proof of principle experiments demonstrate that gene therapy technology could be utilized to successfully purge leukemia cells from HPC.

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Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter.

Abstract: The high molecular weight mucin-like glycoprotein

Cited by 104 publications

References 29 publications

A strategy for enhancing the transcriptional activity of weak cell type-specific promoters

A strategy for enhancing the transcriptional activity of weak cell type-specific promoters

Transgene expression of α tumor necrosis factor with mutations D142N and A144R under control of human telomerase reverse transcriptase promoter eradicates well-established tumors and induces long-term antitumor immunity

Development of a gene therapy based bone marrow purging system for leukemias

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