Gene therapy: X-SCID transgene leukaemogenicity.
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.
Thrasher
Adrian J
AJ
Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK. a.thrasher@ich.ucl.ac.uk
Gaspar
H Bobby
HB
Baum
Christopher
C
Modlich
Ute
U
Schambach
Axel
A
Candotti
Fabio
F
Otsu
Makoto
M
Sorrentino
Brian
B
Scobie
Linda
L
Cameron
Ewan
E
Blyth
Karen
K
Neil
Jim
J
Abina
Salima Hacein-Bey
SH
Cavazzana-Calvo
Marina
M
Fischer
Alain
A
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000209:etiology* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000628:therapy*; D019076:Transgenes / Q000235:genetics*
D015513:Oncogene Proteins; D015375:Receptors, Interleukin-2