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Suicidal gene therapy in the effective control of primary human hepatocellular carcinoma as monitored by noninvasive bioimaging

Gene Therapy volume 19, pages 532–542 (2012)Cite this article

A Corrigendum to this article was published on 06 September 2012

Abstract

Hepatocellular carcinoma (HCC) is usually refractory to the available treatments. For cancer gene therapy purposes, real-time imaging of therapeutic gene expression is of great importance because there are multiple factors that modulate the therapeutic gene expression in a complex tumor microenvironment. As a consequence, multiple doses of therapeutic viral vectors may be required for improved efficacy. In the present study, the luciferase reporter gene and the yeast cytosine deaminase (yCD) genes were bicistronically expressed using the foot-and-mouth disease virus 2A peptide under the regulation of the cytomegalovirus (CMV) promoter. The effectiveness of the yCD/5-FC (5-fluorocytosine) killing efficacy mediated by the herpes simplex virus type 1 (HSV-1) amplicon viral vector was shown using HCC and non-HCC cell lines in vitro. In addition, in vivo experiment also showed tumor regression of a primary HCC 26-1004 tumor xenograft in tumor expressing high levels of the yCD gene (as determined by noninvasive imaging) after intratumoral injection of 1.5 × 106 TU HGCX-L2C HSV-1 amplicon viral vector and 5-FC administration. The HSV-1 amplicon viral vector coupled with the yCD/5-FC prodrug activated suicide gene could potentially be of use in clinical gene therapy for HCC.

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Acknowledgements

We thank Dr Ivy Ho and Mr Berwini Endaya for useful discussions. This work was supported by grant from the National Medical Research Council (NMRC).

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Authors and Affiliations

  1. Cellular and Molecular Research Division, Laboratory of Cancer Gene Therapy, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore

    K C Sia & P Y P Lam

  2. Cellular and Molecular Research Division, Laboratory of Molecular Endocrinology, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore

    H Huynh

  3. Tumor Immunology, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    N Chinnasamy

  4. Cellular and Molecular Research Division, Bek Chai Heah Laboratory of Cancer Genomics, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore

    K M Hui

  5. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    P Y P Lam

  6. Cancer and Stem Cells Biology Program, Duke-NUS Graduate Medical School, Singapore

    P Y P Lam

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Sia, K., Huynh, H., Chinnasamy, N. et al. Suicidal gene therapy in the effective control of primary human hepatocellular carcinoma as monitored by noninvasive bioimaging. Gene Ther 19, 532–542 (2012). https://doi.org/10.1038/gt.2011.131

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