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Targeting proliferating tumor cells via the transcriptional control of therapeutic genes

Cancer Gene Therapy volume 13, pages 44–52 (2006)Cite this article

Abstract

We have previously reported the construction of a cell cycle-regulated HSV-1 amplicon vector (denoted as pC8-36) that confers luciferase reporter gene activities dependent on cellular divisions. However, luciferase reporter gene is well known for its relatively high sensitivity, thus, it is crucial to evaluate the therapeutic efficacy of a transcriptional targeted vector. In this report, we have engineered the FasL and FADD genes into pC8-36 and demonstrated their efficacy for the treatment of human gliomas in vitro and in vivo. Using trypan blue dye exclusion and TUNEL assay, FasL expression mediated by pC8-36 was shown to induce a significantly higher percentage of cell death in proliferating cells than those observed in the G1-arrested cells. The observed cell killing effect correlated well with the level of FasL protein expression when analyzed by ELISA assay. Furthermore, the incorporation of both FasL and FADD into pC8-36 resulted in the enhancement of apoptosis in the target glioma cells both in vitro and in vivo. Targeting proliferating tumor cells via the transcriptional control of therapeutic genes could potentially improve the safety and efficacy of cancer gene therapy, and thus would allow the development of strategies for more effective anticancer therapies.

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Acknowledgements

We thank Dr R Müller (Institute of Molecular Biology and Tumor Research, Germany) for providing us with the plasmids GalcycA, Dr MV Clement (National University of Singapore) for providing us the FADD cDNA and Dr Nai-dy Wang (National University of Singapore) for valuable discussions. This research was supported by grants from the Singapore National Medical Research Council (NMRC) and Singapore Biomedical Research Council (BMRC).

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  1. Division of Cellular and Molecular Research, Gene Vector Laboratory, National Cancer Centre, Singapore, Singapore

    I A W Ho, K M Hui & P Y P Lam

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  1. I A W Ho
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  2. K M Hui
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Correspondence to P Y P Lam.

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Ho, I., Hui, K. & Lam, P. Targeting proliferating tumor cells via the transcriptional control of therapeutic genes. Cancer Gene Ther 13, 44–52 (2006). https://doi.org/10.1038/sj.cgt.7700864

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