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  • Original Article
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Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

Abstract

In this study, we took advantage of the overexpression of human epidermal growth factor receptor 2 (HER-2) in prostate cancers to design lentiviruses with modified envelope proteins that bind antibodies to specific cell-surface antigens. When bound to trastuzumab (Herceptin, Genentech, CA), lentiviruses were able to selectively infect androgen-sensitive LNCaP and castration-resistant C4-2 human prostate cancer cell lines, both of which express high levels of HER-2. To test for a therapeutic effect, we engineered our antibody-binding lentiviruses to express thymidine kinase, which can convert the non-toxic pro-drug ganciclovir (GCV) into a cytotoxic form. LNCaP and C4-2 cells infected by these viruses were sensitive to GCV killing. In vivo, C4-2 xenograft tumors treated either intratumorally or i.v. with trastuzumab-bound lentivirus expressed luciferase, although the latter route was less tumor specific. When a prostate-specific promoter for governing luciferase expression was combined with trastuzumab-mediated delivery, there was a further enrichment in targeting viral gene expression in prostate tumors. In conclusion, we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody.

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Acknowledgements

This work was supported by grants from the Terry Fox Foundation. M Moussavi is supported by a US DOD studentship. The authors also thank Rowena Lee of BC Cancer Agency for providing us trastuzumab and Dr Dieter Fink for providing firefly luciferase expression vectors.

The above work was supported by grants from Terry Fox Foundation of Canada.

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Correspondence to P S Rennie.

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Zhang, Kx., Moussavi, M., Kim, C. et al. Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells. Cancer Gene Ther 16, 820–831 (2009). https://doi.org/10.1038/cgt.2009.28

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  • DOI: https://doi.org/10.1038/cgt.2009.28

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