The evolution of gene therapy in X-linked severe combined immunodeficiency.
OBJECTIVE
To review the evolution of gene therapy in infants with X-linked severe combined immunodeficiency (XL-SCID) and to evaluate the current challenges facing this evolving field.


METHODS
The MEDLINE, OVID, CINAHL, and HealthSTAR databases were searched to identify pertinent articles using the following keywords: gene therapy, XL-SCID, bone marrow transplant, and viral vectors.


METHODS
Journal articles were selected for their relevance to human gene therapy in patients with XL-SCID.


RESULTS
Gene therapy with a retrovirus-derived vector has been used to treat 20 patients with XL-SCID internationally. Although most patients derived improvements in T- and B-cell immune numbers and function, severe adverse effects have occurred. After gene therapy, 5 of the 20 patients developed leukemia. This outcome has been associated with insertion of the corrected gene near the T-cell proto-oncogene LMO2. One of the 5 patients subsequently died.


CONCLUSIONS
Within the past decade, effective improvements in vectorology and cell culture conditions have resulted in clinical success in some infants with SCID and have revived interest after many years of setbacks. However, clinical success and significant adverse events have been reported in patients with XL-SCID who have undergone gene therapy using a retroviral vector. As extensive research into improving safety through vector development and monitoring of gene therapy continues, further progress in gene therapy development can be anticipated.
Rans
Tonya S
TS
Department of Allergy and Immunology, Wilford Hall Medical Center, San Antonio, Texas, USA. Tonya.rans@nellis.af.mil
England
Ronald
R
D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods / Q000639:trends*; D005822:Genetic Vectors / Q000235:genetics; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000090063:Proto-Oncogene Mas; D014780:Viruses / Q000235:genetics; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics* / Q000276:immunology / Q000628:therapy*