819: Gene Therapy for Prostate Cancer by Controlling Adenovirus E1a and E4 Gene Expression with PSES Enhancer

Xiong, Li; Zhang, Yanping; Bae, Kyung-Hee; Stantz, Keith M.; Lee, Sang-Jin; Jung, Chang-Yeol; Juan,; Jemenez, A.; Jeng, Meei-Huey; Kao, Chinghai; Gardener, Thomas A.

doi:10.1016/s0022-5347(18)34988-7

Cited by 26 publications

(70 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells and Cell Culture MCF10A, MCF12A, PC-3, DU145, and HEK293 (transformed human embryonic kidney cell line that expresses complementing adenoviral E1 protein supporting the replication of E1-deleted recombinant adenoviruses) were cultured as described previously (41). MDA-MB-435S, T47D, and PER.C6 [a packaging cell line containing the adenovirus 5 (Ad5) E1a-and E1b-encoding sequences (nucleotides 459 -3,510) under the control of the human phosphoglycerate kinase promoter] were cultured in DMEM containing 10% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

“…Each cell line was infected with standardized doses of virus according to the luciferase activity obtained above to achieve similar infectivity. Cell lysates were collected for Western blot analysis as described previously (41). The membrane was probed with an anti-Ad5 E1a antibody (BD Biosciences PharMingen, San Diego, CA) followed by a horseradish peroxidase-conjugated anti-mouse IgG secondary antibody (Santa Cruz Biotechnology, Santa Cruz, CA).…”

Section: Construction and Amplification Of Recombinant Adenovirusmentioning

confidence: 99%

“…The media were changed 24 hours later, and the viral supernatants were harvested 3 days after the infection. Then, the titers of the harvested virus supernatants were checked by titer assay using HEK293 cells (41). HEK293 cells were seeded in 96-well plates (5 Â 10 3 per well) 1 day before infection.…”

Section: Construction and Amplification Of Recombinant Adenovirusmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by α-lactalbumin promoter

Zhang

Gao

et al. 2005

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

The breast-specific antigen A-lactalbumin is expressed in >60% of breast cancer tissues. To evaluate the effect of gene therapy for breast cancer by controlling adenovirus replication with human A-lactalbumin promoter, we investigated the activity of a 762-bp human A-lactalbumin promoter. A-Lactalbumin promoter showed significantly higher activity in MDA-MB-435S and T47D breast cancer cells than in normal breast cell lines or other tumor cell lines. We then developed two novel breast cancer -restricted replicative adenoviruses, AdALAE1a and AdE1aALAE1b. In AdALAE1a, expression of adenoviral E1a gene is under the control of A-lactalbumin promoter, and in AdE1aALAE1b, expression of both E1a and E1b genes is under the control of a single A-lactalbumin promoter. Both breast cancer -restricted replicative adenoviruses showed viral replication efficiency and tumor cell-killing capability similar to wild-type adenovirus in MDA-MB-435S and T47D cells. The replication efficiency and tumor cell-killing capability of both viruses were attenuated significantly in cells that did not support A-lactalbumin promoter. AdE1aALAE1b showed better breast cancer -restricted replication than AdALAE1a, suggesting that a transcriptional targeting modality with A-lactalbumin promoter controlling both E1a and E1b gene expression is superior to A-lactalbumin promoter controlling only E1a gene expression. Importantly, we found that AdE1aALAE1b could be used to target hormone-independent breast tumors in vivo by inhibiting the growth of MDA-MB-435S s.c. tumors. These data showed that A-lactalbumin promoter could regulate the replication of adenovirus to target hormoneindependent breast cancers, suggesting that A-lactalbumin promoter can be used to develop a novel therapeutic modality for hormone-independent breast cancer. [Mol Cancer Ther 2005;4(12):1850 -9]

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Construction and Amplification Of Recombinant Adenovirusmentioning

confidence: 99%

Section: Construction and Amplification Of Recombinant Adenovirusmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by α-lactalbumin promoter

Zhang

Gao

et al. 2005

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Various approaches have been used to improve the tumor-selectivity and potency of oncolytic viruses, including efforts to place E1a and E1b under the control of distinct tumor-specific heterologous promoters. 13,14,16,17 However, these vectors have suffered from leaky transcription of E1a and E1b and decreased viral replication and cytolytic activity compared with wild-type Ad5.…”

Section: Discussionmentioning

confidence: 99%

“…One approach that we and others have taken for making oncolytic viruses has been to insert tumor-selective promoter elements upstream of critical transcription units including E1a, E1b and E4. [13][14][15][16][17][18] Incorporation of heterologous promoter elements, such as the promoter for prostate-specific antigen, carcinogenic-embryonic antigen, E2F1 and telomerase, has achieved variable levels of tumor-selective replication. The potential clinical utility of viruses using heterologous promoters to provide tumor-selective replication has been limited by nonselective and leaky gene expression, diminished capacity of these vectors to replicate when compared with the wild-type virus and recombination events due to the heterologous promoter sequence.…”

Section: Introductionmentioning

confidence: 99%

Deletion analysis of Ad5 E1a transcriptional control region: impact on tumor-selective expression of E1a and E1b

Hedjran¹,

Shantanu²,

Tony³

2011

Cancer Gene Ther

View full text Add to dashboard Cite

The regulatory sequences upstream of E1a, the first viral protein expressed upon infection of cells with adenovirus, have binding sites for multiple transcription factors including two binding sites for E2f and five binding sites for Pea3. We evaluated the impact of deletions, which remove one or more of these transcription factor-binding sites on the expression of E1a in a panel of tumor cells and non-transformed cells. We demonstrated that specific deletions in the E1a enhancer markedly reduced the expression of E1a in growth-arrested cells while having a minimal impact on the expression of E1a in a panel of tumor cells. In particular, deletion of a 50-bp region located from À305 to À255 upstream of the E1a initiation site resulted in marked reduction of E1a and E1b expression and cytolytic activity in growth-arrested cells, while retaining near wild-type of expression of E1a and E1b and cytolytic activity in tumor cells. This deletion removed two Pea3 sites and one E2f site. The characteristics of this vector, TAV-255, was compared with dl1520 (Onyx-015) and demonstrated restricted cytolytic activity in growth-arrested cells similar to dl1520 and superior cytolytic activity in a panel of tumor cell lines. In this current study, we demonstrate that TAV-255, an E1a enhancer deletion vector, possesses tumor selective expression of both E1a and E1b along with potent tumor-selective oncolytic activity.

show abstract

Oncolytic viral therapy for human cancer: Challenges revisited

Tong

2005

Drug Dev. Res.

View full text Add to dashboard Cite

Conditional replicative, oncolytic adenoviruses are genetically modified to replicate primarily in malignant cells with oncogenetic defects, selectively killing cancer cells in the process. Viral progenies released within the tumor microenvironment can penetrate, infect, and destroy additional cell layers of the solid tumor mass. Much excitement has been generated over the clinical successes of ONYX-015 adenovirus treatment for advanced head and neck cancer, pancreatic carcinoma, and metastatic colorectal carcinoma at the locoregional level. However, follow-up trials with systemic viral administration have not met initial expectations. This review examines recent basic science developments that may potentially overcome the two key limitations of systemic virotherapy, namely, suboptimal tumor oncolysis and pharmacokinetic shortcomings due to rapid viral clearance. Late-generation constructs incorporate alternative viral backbone modifications and antitumor transgenes to enhance oncolytic potency. Furthermore, altered viral tropism, through masking or substitution of viral surface components, is likely to promote tumor-selective targeting and safety. Merits of these approaches in the clinical arena are discussed. Drug Dev.

show abstract

819: Gene Therapy for Prostate Cancer by Controlling Adenovirus E1a and E4 Gene Expression with PSES Enhancer

Cited by 26 publications

References 0 publications

Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by α-lactalbumin promoter

Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by α-lactalbumin promoter

Deletion analysis of Ad5 E1a transcriptional control region: impact on tumor-selective expression of E1a and E1b

Oncolytic viral therapy for human cancer: Challenges revisited

Contact Info

Product

Resources

About