This project involves the conduct of a therapeutic clinical trial using autologous blood stem cell targeted gene therapy to treat X-linked severe combined immune deficiency. 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 (gc) of receptors for interleukins (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(s) from a parent. Subjects received retrovirus transduced autologous peripherally mobilized CD34+ hematopoietic cells. Initial multi-lineage retroviral marking and improvements in health occurred in all 3 children, and T cell function significantly improved in the youngest subject (age 10 years). Long term benefit appears to have occurred only in this youngest patient, though all three remain gene marked. Further follow-up of clinical, immunologic and molecular parameters in our patients will establish the long-term safety and efficacy of this approach to gene therapy for pre-adolescents with XSCID who have failed to achieve or maintain immune reconstitution after BMT.
| De Ravin, Suk See; Malech, Harry L (2009) Partially corrected X-linked severe combined immunodeficiency: long-term problems and treatment options. Immunol Res 43:223-42 |
| De Ravin, Suk See; Shum, Elaine; Zarember, Kol A et al. (2008) Short stature in partially corrected X-linked severe combined immunodeficiency--suboptimal response to growth hormone. J Pediatr Endocrinol Metab 21:1057-63 |
| Chinen, Javier; Davis, Joie; De Ravin, Suk See et al. (2007) Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency. Blood 110:67-73 |
| Shearer, William T; Malech, Harry L; Puck, Jennifer M (2007) Primary immunodeficiency: meeting the challenges. J Allergy Clin Immunol 120:753-5 |
| Puck, Jennifer M; Malech, Harry L (2006) Gene therapy for immune disorders: good news tempered by bad news. J Allergy Clin Immunol 117:865-9 |
