Indraccolo, Stefano and Habeler, Walter and Tisato, Veronica and Stievano, Laura and Piovan, Erich and Tosello, Valeria and Esposito, Giovanni and Wagner, Ralf and Uberla, Klaus and Chieco-Bianchi, Luigi and Amadori, Alberto (2002) Gene transfer in ovarian cancer cells: A comparison between retroviral and lentiviral vectors. CANCER RESEARCH, 62 (21). pp. 6099-6107. ISSN 0008-5472
Full text not available from this repository.Abstract
Local gene therapy could be a therapeutic option for ovarian carcinoma, a life-threatening malignancy, because of disease containment within the peritoneal cavity in most patients. Lentiviral vectors, which are potentially capable of stable transgene expression, may be useful to vehicle therapeutic molecules requiring long-term production in these tumors. To investigate this concept, we used lentiviral vectors to deliver the enhanced green fluorescent protein (EGFP) gene to ovarian cancer cells. Their efficiency of gene transfer was compared with that of a retroviral vector carrying the same envelope. In vitro, both vectors infected ovarian cancer cells with comparable efficiency under standard culture conditions; however, the lentiviral vector was much more efficient in transducing growth-arrested cells when compared with the retroviral vector. Gene transfer was fully neutralized by an anti-VSV-G antibody, and in vitro stability was similar. In vivo, the lentiviral vector delivered the transgene 10-fold more efficiently to ovarian cancer cells growing i.p. in SCID mice, as evaluated by real-time PCR analysis of the tumors. Confocal microscopy analysis of tumor sections showed a dramatic difference at the level of transgene expression, because abundant EGFP(+) cells were detected only in mice receiving the lentiviral vector. Quantitative analysis by flow cytometry confirmed this and indicated 0.05 and 5.6% EGFP(+) tumor cells after administration of the retroviral and lentiviral vector, respectively. Injection of ex vivo transduced tumor cells, sorted for EGFP expression, indicated that the lentiviral vector was considerably more resistant to in vivo silencing in comparison with the retroviral vector. Finally, multiple administrations of a murine IFN-alpha(1)-lentiviral vector to ovarian carcinoma-bearing mice significantly prolonged the animals' survival, indicating the therapeutic efficacy of this approach. These findings indicate that lentiviral vectors deserve attention in the design of future gene therapy approaches to ovarian cancer aimed at achieving long-term expression of therapeutic genes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SIMIAN IMMUNODEFICIENCY VIRUS; ADENOVIRAL-MEDIATED DELIVERY; SINGLE-CHAIN ANTIBODY; PHASE-I TRIAL; THERAPY; GANCICLOVIR; EXPRESSION; CARCINOMA; TRANSDUCTION; RESISTANCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Sep 2021 07:13 |
| Last Modified: | 29 Sep 2021 07:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39708 |
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