Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase–mediated suicide gene therapy (original) (raw)

Cancer Gene Therapy volume 8, pages 137–144 (2001)Cite this article

Abstract

To evaluate human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase (HSV-TK)–mediated gene therapy, we tested the utility of different viral vectors on three human cell lines DU-145, LNCaP, and PC-3. Our viral vectors were carrying a fusion gene of HSV-TK and green fluorescent protein for accurate determination of the gene transfer rate and its contribution to the treatment outcome in each case. We observed that adenoviral and lentiviral vectors were efficient vehicles for all the cell lines, whereas Semliki Forest virus and Sindbis virus vectors yielded only a few percent of transgene-positive cells. Despite sufficient gene transfer rates (25–45%) in the ganciclovir (GCV) sensitivity experiment, only DU-145 cells were efficiently destroyed under clinically relevant GCV concentrations. This was shown to be due to low level of “bystander effect” in PC-3 and LNCaP cells. Our data demonstrate that human prostate tumors can be good targets for adenovirus- or lentivirus-mediated HSV-TK/GCV gene therapy, but each tumor should be investigated for gene transfer rate and bystander effect to warrant a sufficient treatment result. Cancer Gene Therapy (2001) 8, 137–144

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Authors and Affiliations

  1. A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland
    Sami Loimas, Marjo-Riitta Toppinen, Juhani Jänne & Jarmo Wahlfors
  2. Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland
    Sami Loimas & Jarmo Wahlfors
  3. Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland
    Tapio Visakorpi

Authors

  1. Sami Loimas
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  2. Marjo-Riitta Toppinen
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  3. Tapio Visakorpi
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  4. Juhani Jänne
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  5. Jarmo Wahlfors
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Correspondence toJarmo Wahlfors.

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Loimas, S., Toppinen, MR., Visakorpi, T. et al. Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase–mediated suicide gene therapy.Cancer Gene Ther 8, 137–144 (2001). https://doi.org/10.1038/sj.cgt.7700286

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