Gene therapy: X-SCID transgene leukaemogenicity

Nature. 2006 Sep 21;443(7109):E5-6; discussion E6-7. doi: 10.1038/nature05219.

Abstract

Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis. Woods et al. forced high expression of the corrective therapeutic gene IL2RG, which encodes the gamma-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.

Publication types

  • Comment

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Clinical Trials as Topic / adverse effects
  • Genetic Therapy / adverse effects*
  • Humans
  • Leukemia / etiology*
  • Leukemia / genetics
  • Mice
  • Mice, SCID
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / therapy*
  • Transgenes / genetics*

Substances

  • Oncogene Proteins
  • Receptors, Interleukin-2