Gene therapy: therapeutic gene causing lymphoma.
The development of T-cell leukaemia following the otherwise successful treatment of three patients with X-linked severe combined immune deficiency (X-SCID) in gene-therapy trials using haematopoietic stem cells has led to a re-evaluation of this approach. Using a mouse model for gene therapy of X-SCID, we find that the corrective therapeutic gene IL2RG itself can act as a contributor to the genesis of T-cell lymphomas, with one-third of animals being affected. Gene-therapy trials for X-SCID, which have been based on the assumption that IL2RG is minimally oncogenic, may therefore pose some risk to patients.
Woods
Niels-Bjarne
NB
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Bottero
Virginie
V
Schmidt
Manfred
M
von Kalle
Christof
C
Verma
Inder M
IM
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002986:Clinical Trials as Topic / Q000009:adverse effects / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D015316:Genetic Therapy / Q000009:adverse effects*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009857:Oncogenes / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000628:therapy*; D013997:Time Factors
D015375:Receptors, Interleukin-2