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- Title
Electroporation-mediated and EBV LMP1-regulated gene therapy in a syngenic mouse tumor model.
- Authors
Hsieh, Yu-hua; Wu, Chang-jer; Chow, Kai-ping; Tsai, Chia-lung; Chang, Yu-sun
- Abstract
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-?B 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, p6?B-EDL1E-tk, containing six copies of the NF-?B 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 p6?B-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 p6?B-EDL1E-tk cassette and GCV via in vivo electroporation, but not in mice treated with p6?B-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 p6?B-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.Cancer Gene Therapy (2003) 10, 626-636. doi:10.1038/sj.cgt.7700609
- Subjects
EPSTEIN-Barr virus; ELECTROPORATION; CYTOLOGICAL techniques
- Publication
Cancer Gene Therapy, 2003, Vol 10, Issue 8, p626
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700609