Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency.
Retroviral gene therapy can restore immunity to infants with X-linked severe combined immunodeficiency (XSCID) caused by mutations in the IL2RG gene encoding the common gamma chain (gammac) of receptors for interleukins 2 (IL-2), -4, -7, -9, -15, and -21. We investigated the safety and efficacy of gene therapy as salvage treatment for older XSCID children with inadequate immune reconstitution despite prior bone marrow transplant from a parent. Subjects received retrovirus-transduced autologous peripherally mobilized CD34(+) hematopoietic cells. T-cell function significantly improved in the youngest subject (age 10 years), and multilineage retroviral marking occurred in all 3 children.
Chinen
Javier
J
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1456, USA.
Davis
Joie
J
De Ravin
Suk See
SS
Hay
Beverly N
BN
Hsu
Amy P
AP
Linton
Gilda F
GF
Naumann
Nora
N
Nomicos
Effie Y H
EY
Silvin
Christopher
C
Ulrick
Jean
J
Whiting-Theobald
Narda L
NL
Malech
Harry L
HL
Puck
Jennifer M
JM
D015316:Genetic Therapy / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007223:Infant; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000008:administration & dosage* / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic; D014182:Transplantation, Autologous; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics / Q000276:immunology* / Q000628:therapy*
D015375:Receptors, Interleukin-2