Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer

Hasenburg, Annette; Tong, Xiao; Rojas-Martínez, Augusto; Nyberg-Hoffman, Cassandra; Kieback, C. C.; Kaplan, Alan L.; Kaufman, Raymond H.; Ramzy, Ibrahim; Aguilar-Córdova, Estuardo; Kieback, D. G.

doi:10.1038/sj.cgt.7700192

Cited by 61 publications

(32 citation statements)

References 17 publications

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“…This suggests that continuous treatment or a combination with other agents is required for the full regression of tumor growth, consistent with previous reports. For example, ponicidin 49 and topotecan 50 were used to enhance killing and the bystander effect for tumor eradication.…”

Section: Discussionmentioning

confidence: 99%

“…To establish an in vivo electroporation protocol, mice muscles were injected with increasing amounts (10,25,50,75, and 100 mg) of pCMV-Luc in a total volume of 50 ml, with or without in vivo electroporation. To monitor transgene expression, luciferase activity was determined on days 1, 2, and 30.…”

Section: Transgene Expression In Tissues By In Vivo Electroporationmentioning

confidence: 99%

“…As shown in Fig 6b, tumor growth was significantly suppressed in the group coinjected with p6kB-EDL1E-tk and GCV (100 mg in a volume of 50 ml) when measured at day 10. Tumor growth in mice electroporated in vivo with p6kB-EDL1E-tk and intraperitoneal delivery of GCV (10,25,50,75, and 100 mg) of pCMV-Luc in a volume of 50 ml were injected into the left and right limb tibial muscles of four mice (n ¼ 8 sites for each treatment or control group). Luciferase activity was detected at 1, 2, and 30 (50 and 100 mg only) days after DNA transfer by in vivo electroporation.…”

Section: Thymidine Kinase Activity In Vivomentioning

confidence: 99%

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Electroporation-mediated and EBV LMP1-regulated gene therapy in a syngenic mouse tumor model

Hsieh

Wu²,

Chow

et al. 2003

Cancer Gene Ther

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Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncogene expressed in EBV-associated nasopharyngeal carcinoma (NPC). Previous studies indicate that a strategy combining LMP1-mediated NF-kB activation and the HSV thymidine kinase/Ganciclovir (HSVtk/GCV) prodrug system leads to regression of tumor growth in nude mice. To improve the efficacy of this strategy in immunocompetent hosts, we developed a therapeutic cassette, p6kB-EDL1E-tk, containing six copies of the NF-kB binding motif and an epithelial-specific EBV promoter, ED-L1E. The cassette was tested in a murine CT-26 carcinoma model in syngenic Balb/c mice. Coinjection of an LMP1-expressing vector and p6kB-EDL1E-tk by in vivo electroporation in mouse muscle revealed at least two-fold higher TK enzymatic activity than that of previously tested pLTR-tk. Furthermore, growth was attenuated in a group of mice containing LMP1-positive tumors that were intratumorally injected with the p6kB-EDL1E-tk cassette and GCV via in vivo electroporation, but not in mice treated with p6kB-EDL1E-tk or GCV alone. Similarly, no retardation of tumor growth was observed in mice containing LMP1-negative CT-26 tumors injected with both the p6kB-EDL1E-tk cassette and GCV. We propose that intratumoral injection of therapeutic agents, such as DNA of transcription-regulated cassette and GCV, via in vivo electroporation may be used as an alternative treatment for EBV LMP1-expressing cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Transgene Expression In Tissues By In Vivo Electroporationmentioning

confidence: 99%

Section: Thymidine Kinase Activity In Vivomentioning

confidence: 99%

See 1 more Smart Citation

Electroporation-mediated and EBV LMP1-regulated gene therapy in a syngenic mouse tumor model

Hsieh

Wu²,

Chow

et al. 2003

Cancer Gene Ther

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“…Tumor cells that express HSV-1 TK are rendered sensitive to pro-drugs, such as acyclovir, due to preferential phosphorylation. This paradigm has been used in multiple antitumor protocols, 22,[39][40][41] and was further tested in the present study. A standard treatment regimen of acyclovir successfully eradicated reporter gene expression from infected vascular tissue.…”

Section: Figure 5 Hsv-1-mediated Prevention Of Restenosis In Rabbit Vmentioning

confidence: 99%

Prevention of restenosis by a herpes simplex virus mutant capable of controlled long-term expression in vascular tissue in vivo

et al. 2001

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Neointimal hyperplasia resulting from vascular smooth muscle cell (SMC) proliferation and luminal migration is the major cause of autologous vein graft failure following vascular coronary or peripheral bypass surgery. Strategies to attenuate SMC proliferation by the delivery of oligonucleotides or genes controlling cell division rely on the use of high concentrations of vectors, and require pre-emptive disruption of the endothelial cell layer. We report a genetically engineered herpes simplex virus (HSV-1) mutant that, in an in vivo rabbit

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“…A number of clinical trials using adenoviral vectors have been performed in EOC with direct intraperitoneal administration. [2][3][4][5][6] Delivery of adenoviral vectors through an intraperitoneal route has been well tolerated in gene therapy trials and the virus has an excellent safety record when used correctly. EOC is generally confined to the peritoneal cavity and, therefore, is ideally suited to intraperitoneal therapy.…”

Section: Introductionmentioning

confidence: 99%

Role of cell surface molecules and autologous ascitic fluid in determining efficiency of adenoviral transduction of ovarian cancer cells

et al. 2010

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Adenovirus is the most frequently used virus in gene therapy clinical trials. There have been conflicting reports on the ability of adenovirus to transduce primary ovarian cancer samples and the expression of relevant cell surface molecules. These factors were examined using primary ovarian cancer cells cultured from ascites and solid tumor to gain insights into the clinical use of adenovirus in ovarian cancer. The level of transduction of primary cultures was much higher than uncultured cells and established cell lines, and correlated with higher levels of coxsackie-adenovirus receptor (CAR) and integrin expression. Growth of primary cultures in autologous ascitic fluid prevented an increase in CAR expression and inhibited transduction compared with cells treated in supplemented RPMI. Cells at the periphery of solid tumor samples were transduced using a replication-incompetent virus and correlated with CAR expression. However, transduction was abolished by autologous ascitic fluid, despite the expression of CAR. We conclude that the use of adenoviruses for ovarian cancer gene therapy will require testing in the presence of inhibitory factors in ascitic fluid. The clinical use of adenoviral vectors may require circumvention of such inhibitory factors and the use of replication competent adenovirus to enable efficient viral penetration of the cancer.

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Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer

Cited by 61 publications

References 17 publications

Electroporation-mediated and EBV LMP1-regulated gene therapy in a syngenic mouse tumor model

Electroporation-mediated and EBV LMP1-regulated gene therapy in a syngenic mouse tumor model

Prevention of restenosis by a herpes simplex virus mutant capable of controlled long-term expression in vascular tissue in vivo

Role of cell surface molecules and autologous ascitic fluid in determining efficiency of adenoviral transduction of ovarian cancer cells

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