Telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate

“…[27][28][29] Therefore, telomerase is a suitable promoter to achieve tumourspecificity of transgene expression due to the difference in telomerase expression between normal and malignant cells. Indeed, previous in vitro studies have already identified telomerase as a potent tumour-specific promoter, 11,12,30 and 80-90% of adenocarcinoma prostate cells, regardless of stage, are telomerase-positive. [13][14][15][16][17][18] Both the human telomerase RNA (hTR) and the human telomerase reverse transcriptase (hTERT) promoters compared favourably with the strong ubiquitous CMV promoter with respect to their ability to drive the expression of the NAT transgene.…”

“…It has previously been shown that the hTR gene is expressed at high levels in cancer cells, yet can also be detected at low levels in some normal tissues, while the hTERT gene is expressed at lower levels in cancer cells and is generally undetectable in normal cells. 12 This suggests that both promoters may be of use for genetic therapies designed to target genes to malignant cells via tumour-specific gene expression.…”

“…[8][9][10] One means of limiting the expression of the NAT transgene to tumour cells is by placing the transgene under the control of a tumour-specific promoter, such as telomerase. 11,12 This is an especially attractive component of gene therapy of prostate cancer since there is increased expression of both the RNA component, human telomerase RNA (hTR), and the protein component, human telomerase reverse transcriptase (hTERT) in cancer cells, including prostate cancer, with little expression in normal cells. [13][14][15][16][17][18] We demonstrate that a targeted tumour-specific radiotherapy/gene therapy strategy with [ 131 I]MIBG for prostate cancer is feasible and could be a promising option for future treatment of prostate cancer.…”

Tumor-specific adenoviral gene therapy: transcriptional repression of gene expression by utilizing p53-signal transduction pathways

“…[1][2][3][4][5][6][7][8][9][41][42][43][44][45][46] In Figure 6 Influence of orientation and distance of the expression cassettes for p53-dependent transcriptional repression in a double transgene adenoviral shuttle plasmid. (d) The CMV gal-5 luciferase reporter cassette and the transcriptional repressor cassettes (GAL4-KRAB-A and GAL4-SIN3B-SF) under control of prMin-RGC were cloned into the adenoviral shuttle plasmid in different orientations as indicated.…”

“…Besides retargeting adenoviral vectors by genetical modifications of the fiber protein, many attempts have been made to target therapy to cancer cells by using tumor selective promoters such as AFP-, CEA-, PSA-or hTERT-promoter. [1][2][3][4][5][6][7][8][9][10] Using this approach, tumor specificity has been achieved at the cost of 50-300-fold loss in transcriptional activity compared to the strong but nonselective CMV-promoter. Other important limitations of gene therapy targeting by tumor-specific promoters are the heterogenous strength of these promoters in different tumor cells within a tumor nodule and the wide variety of promoter activities in different tumors.…”