Abstract
We have constructed a prostate-specific lentiviral vector based on the promoter of the prostate-specific antigen (PSA). The PSA promoter-based lentiviral vector has been used to deliver the diphtheria toxin A (DTA) gene into prostate cancer cells, and has shown promising tissue-specific eradication of prostate cancer cells in cell culture. To evaluate the efficacy of eradicating human prostate cancer cells in vivo, we used human LNCaP prostate xenografts in nude mice as an animal model and found that with a single injection of the DTA lentiviral vector into LNCaP prostate tumors, approximately 75% of the tumors (from three experiments; conducted 9/11, 11/15 and 3/4) in the animals were completely eradicated. The DTA vector has also shown the ability to cause tumor regression in recurrent prostate tumors. Intravenous injection of the DTA lentiviral vector into nude mice elicited no pathogenic effects, suggesting that this prostate tissue-specific vector is safe for eradicating prostate cancer cells in vivo.
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Acknowledgements
We thank Dr ISY Chen for providing the pCMVΔR8.2vprx plasmid, and W Aft for editing and preparing the manuscript.
The work described in this publication was made possible by funds received from the Cancer Research Fund under Interagency Agreement #97-12013 (University of California, Davis contract #98-00924V) with the Department of Health Services, Cancer Research Section; National Institutes of Health grant CA66022 (J-y Zheng and SP); and US Department of Defense grant DAMD17-99-1-9033 (DY and SP).
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Zheng, Jy., Chen, D., Chan, J. et al. Regression of prostate cancer xenografts by a lentiviral vector specifically expressing diphtheria toxin A. Cancer Gene Ther 10, 764–770 (2003). https://doi.org/10.1038/sj.cgt.7700629
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DOI: https://doi.org/10.1038/sj.cgt.7700629
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