X-SCID transgene leukaemogenicity (original) (raw)

Gene therapy

Nature volume 443, pages E5–E6 (2006)Cite this article

Abstract

Arising from: Woods, N.-B., Bottero, V., Schmidt, M., von Kalle, C. & Verma, I. M. Nature 440, 1123 (2006); see also communication from Pike-Overzet et al.; Woods et al. reply

Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency1,2,3, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis4. Woods et al.5 forced high expression of the corrective therapeutic gene IL2RG, which encodes the γ-chain of the interleukin-2 receptor, in a mouse model of the disease and found that tumours appeared in a proportion of cases. Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated.

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Authors and Affiliations

  1. Molecular Immunology Unit, Institute of Child Health, University College London, London, WC1N 1EH, UK
    Adrian J. Thrasher & H. Bobby Gaspar
  2. Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK
    Adrian J. Thrasher & H. Bobby Gaspar
  3. Department of Experimental Hematology, Hannover Medical School, Hannover, 30625, Germany
    Christopher Baum, Ute Modlich & Axel Schambach
  4. Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, 45229-3039, Ohio, USA
    Christopher Baum
  5. Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA
    Fabio Candotti
  6. Center for Experimental Medicine, University of Tokyo, Tokyo, 108-8639, Japan
    Makoto Otsu
  7. Department of Hematology/Oncology, Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, 38105, Tennessee, USA
    Brian Sorrentino
  8. Division of Pathological Sciences, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, G61 1QH, UK
    Linda Scobie, Ewan Cameron, Karen Blyth & Jim Neil
  9. INSERM Unit 768, Hôpital Necker, Assistance Publique–Hôpitaux de Paris, Paris, 75743, France
    Salima Hacein-Bey Abina, Marina Cavazzana-Calvo & Alain Fischer
  10. Département de Biothérapies, Assistance Publique–Hôpitaux de Paris, Paris, 75743, France
    Salima Hacein-Bey Abina & Marina Cavazzana-Calvo
  11. Faculté de Médecine, Université René Descartes, Paris, 75270, France
    Marina Cavazzana-Calvo & Alain Fischer
  12. Unité d'Immuno-Hématologie Pédiatrique, Assistance Publique–Hôpitaux de Paris, Paris, 75743, France
    Alain Fischer

Authors

  1. Adrian J. Thrasher
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  2. H. Bobby Gaspar
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  3. Christopher Baum
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  4. Ute Modlich
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  5. Axel Schambach
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  6. Fabio Candotti
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  7. Makoto Otsu
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  8. Brian Sorrentino
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  9. Linda Scobie
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  10. Ewan Cameron
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  11. Karen Blyth
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  12. Jim Neil
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  13. Salima Hacein-Bey Abina
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  14. Marina Cavazzana-Calvo
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  15. Alain Fischer
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Thrasher, A., Gaspar, H., Baum, C. et al. X-SCID transgene leukaemogenicity.Nature 443, E5–E6 (2006). https://doi.org/10.1038/nature05219

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