A gene-therapy treatment for a severe immune deficiency could contribute to the later development of T-cell lymphomas, according to a Brief Communication in the 27 April 2006 issue of Nature (Vol. 440, No. 7088, p. 1123) this week. Inder M. Verma and colleagues argue, on the basis of their findings in mice, that preclinical treatments involving transgenes should include long-term follow-up before entering clinical trial.
The team demonstrate that one-third of mice treated for X-linked severe combined immune deficiency (X-SCID) with the corrective therapeutic gene IL2RG go on to develop T-cell lymphomas. They show that the origin of these tumours is not, as previously believed, due to the upregulated expression of an oncogene but is related to IL2RG itself.
The syndrome X-SCID is caused by faulty expression of IL2RG, a component of the receptor for interleukin-2, which results in diminished lymphoid cell survival and proliferation. Gene therapy can restore the expression of IL2RG and improve adaptive immunity in patients.
Until now IL2RG has not been considered to be oncogenic but the researchers argue that this is because studies have not been lengthy enough to pick up on these effects. They warn that the preclinical phases of gene therapy treatments should include follow-up over a much longer term.
Inder Verma (The Salk Institute for Biological Studies, La Jolla, CA, USA)
(C) Nature press release.
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