Gene Therapy Clinical Trials for X-linked Severe Combined Immunodeficiency

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Abstract

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 from a parent. Subjects received retrovirus transduced autologous peripherally mobilized CD34+ hematopoietic cells. 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 occured 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.