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Gene therapy for malignant mesothelioma: beyond the infant years

Cancer Gene Therapy volume 13, pages 897–904 (2006)Cite this article

Abstract

Mesothelioma may be particularly well suited for gene therapy treatment owing to its accessibility, allowing both intrapleural and intratumoral gene delivery. At least four gene therapy trials have been carried out in mesothelioma patients, using different vector systems (adenovirus, vaccinia virus, irradiated tumor cells), and different transgenes (herpes simplex virus thymidine kinase (HSVtk) combined with ganciclovir, IL-2, IFN-β). Although small in scale, these trials have given an inkling of hope for therapeutic efficacy. However, it is clear that gene therapy protocols need to be optimized further. This paper will review progress made in (i) vector development, (ii) defining optimal transgenes, and (iii) gene delivery. Adenoviruses are the most commonly used vectors for gene therapy, and are continuously being improved. With respect to the nature of the transgenes, five categories can be distinguished: (i) ‘suicide’ or sensitivity genes (e.g., HSVtk), (ii) cytokines and other immune modulators, (iii) replacements for mutant tumor suppressor genes (e.g., p53), (iv) antiangiogenic proteins and (v) tumor antigens. It seems clear that expression of a single transgene is unlikely to be sufficient to eradicate a tumor, such as mesothelioma, that is diagnosed late in disease progression. Hence, multimodality therapy, including conventional therapy (chemo- and radiotherapy, surgery) with one or more transgenes has a higher chance of success.

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Authors and Affiliations

  1. School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia

    R G van der Most, B W S Robinson & D J Nelson

  2. Western Australian Institute of Medical Research, Nedlands, Western Australia, Australia

    R G van der Most

  3. School of Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia

    D J Nelson

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  1. R G van der Most
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  2. B W S Robinson
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  3. D J Nelson
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Correspondence to R G van der Most.

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van der Most, R., Robinson, B. & Nelson, D. Gene therapy for malignant mesothelioma: beyond the infant years. Cancer Gene Ther 13, 897–904 (2006). https://doi.org/10.1038/sj.cgt.7700935

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  • DOI: https://doi.org/10.1038/sj.cgt.7700935

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