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Replicative retroviral vectors for cancer gene therapy

Cancer Gene Therapy volume 10, pages 30–39 (2003)Cite this article

Abstract

Poor efficiency of gene transfer into cancer cells constitutes the major bottleneck of current cancer gene therapy. We reasoned that because tumors are masses of rapidly dividing cells, they would be most efficiently transduced with vector systems allowing transgene propagation. We thus designed two replicative retrovirus-derived vector systems: one inherently replicative vector, and one defective vector propagated by a helper retrovirus. In vitro, both systems achieved very efficient transgene propagation. In immunocompetent mice, replicative vectors transduced >85% tumor cells, whereas defective vectors transduced <1% under similar conditions. It is noteworthy that viral propagation could be efficiently blocked by azido-thymidine, in vitro and in vivo. In a model of established brain tumors treated with suicide genes, replicative retroviral vectors (RRVs) were approximately 1000 times more efficient than defective adenoviral vectors. These results demonstrate the advantage and potential of RRVs and strongly support their development for cancer gene therapy.

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Acknowledgements

We thank FL Cosset for helpful comments. We also thank A Morel and F Foata for their participation in some initial experiments. This work was supported by the Université Pierre et Marie Curie (UPMC), Centre National de la Recherche Scientifique (CNRS), European Grant QLK3-CT-1999-00364 Génopoïétic, Association Française contre les Myopathies (AFM), Association pour la Recherche sur les Déficits Immunitaires Viro-Induits, and Assistance Publique — Hôpitaux de Paris.

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Authors and Affiliations

  1. Biologie et Thérapeutique des Pathologies Immunitaires, CNRS/UPMC UMR 7087, Hôpital Pitié-Salpêtrière, Paris, France

    Sounkary K Solly, Stephane Trajcevski, Charlotte Frisén, Georg W Holzer, Béatrice Clerc & David Klatzmann

  2. Génopoïétic SA, Paris, France

    Stephane Trajcevski & Elisabeth Nelson

  3. Molecular Medicine and Gene Therapy Unit, University of Manchester, Manchester, UK

    Evelyn Abordo-Adesida

  4. Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Maria Castro & Pedro Lowenstein

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  1. Sounkary K Solly
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Correspondence to David Klatzmann.

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Solly, S., Trajcevski, S., Frisén, C. et al. Replicative retroviral vectors for cancer gene therapy. Cancer Gene Ther 10, 30–39 (2003). https://doi.org/10.1038/sj.cgt.7700521

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