Abstract
The use of conditionally replicating adenoviruses offers an attractive complementary treatment strategy for localized prostate cancer. We have produced a replicating adenovirus, Ad[I/PPT-E1A], where E1A gene expression is controlled by a recombinant regulatory sequence designated PPT. The PPT sequence comprises a PSA enhancer, a PSMA enhancer and a T-cell receptor γ-chain alternate reading frame protein promoter, and it is shielded from transcriptional interference from adenoviral backbone sequences by an H19 insulator. Ad[I/PPT-E1A] yields prostate-specific E1A protein expression, viral replication and cytolysis in vitro. Furthermore, Ad[I/PPT-E1A] considerably regresses the growth of subcutaneous LNCaP prostate cancer tumors in nude mice. Importantly, the viral replication and cytolytic effect of Ad[I/PPT-E1A] are independent of the testosterone levels in the prostate cancer cells. This may be beneficial in a clinical setting since many prostate cancer patients are treated with androgen withdrawal. In conclusion, Ad[I/PPT-E1A] may prove to be useful in the treatment of localized prostate cancer.
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Acknowledgements
We thank Dr Valeria Giandomenico for technical advices and fruitful discussions. This work was supported by the Swedish Cancer Society (Grant 4419-B03-04XBB) and the European Community on behalf of the Prostate Cancer: Initiative for Gene Therapy group (Grant QLK6-CT-2000-00271).
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Cheng, WS., Dzojic, H., Nilsson, B. et al. An oncolytic conditionally replicating adenovirus for hormone-dependent and hormone-independent prostate cancer. Cancer Gene Ther 13, 13–20 (2006). https://doi.org/10.1038/sj.cgt.7700881
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DOI: https://doi.org/10.1038/sj.cgt.7700881
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