Gene therapy for scid trial#

Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Gene therapy of RAG-2−/− mice: sustained correction of the immunodeficiency. Self-selection by genetically modified committed lymphocyte precursors reverses the phenotype of JAK3-deficient mice without myeloablation. Mol Ther 2003 7: S448.īunting KD, Lu T, Kelly PF, Sorrentino BP. Correction of the immune and metabolic defect of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Corrective gene transfer into bone marrow CD34+ cells for adenosine deaminase (ADA) deficiency: results in four patients after one year of follow-up. Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement. Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates. Persistence and expression of the adenosine deaminase gene for twelve years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial. American Society of Gene Therapy's Sixth Annual Meeting Executive Summaries, Vol. Immune Recovery Following Retroviral Mediated Common Gamma Chain Gene Therapy for X-linked Severe Combined Immunodeficiency. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1 ((gamma) c deficiency). Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. Optimization of retroviral gene transfer protocol to maintain the lymphoid potential of progenitor cells. A defined window for efficient gene marking of severe combined immunodeficient-repopulating cells using a gibbon ape leukaemia virus-pseudotyped retroviral vector. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Nat Rev Immunol 2001 3: 200–208.Ĭavazzana-Calvo M et al. Primary immunodeficiency diseases: an experimental model for molecular medicine.

Gene therapy for scid trial#

This trial was registered at as #NCT00794508.Fischer A. These long-term findings demonstrate enduring efficacy of GT for ADA SCID but also highlight risks of genotoxicity with gRVs. No patient experienced a leukoproliferative event after GT, despite persisting prominent clones with vector integrations adjacent to proto-oncogenes. Outcomes were generally better in younger patients and those receiving higher doses of gene-marked CD34 + cells. There were broad ranges of responses in normalization of ADA enzyme activity and adenine metabolites in blood cells and levels of cellular and humoral immune reconstitution. Four of 9 evaluable patients with the highest gene marking and B-cell numbers remain off immunoglobulin replacement therapy and responded to vaccines. ERT was restarted 6 months after GT in the oldest patient who had no evidence of benefit from GT. Nine of 10 patients have sufficient immune reconstitution to protect against serious infections and have not needed to resume ERT or proceed to secondary allogeneic HSCT. These patients were monitored in a long-term follow-up protocol over 8 to 11 years. Autologous bone marrow CD34 + cells were transduced ex vivo with the MND ( myeloproliferative sarcoma virus, negative control region deleted, dl587rev primer binding site)–ADA gammaretroviral vector (gRV) and infused following busulfan reduced-intensity conditioning.

A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a phase 2 clinical trial between 20. Patients lacking functional adenosine deaminase activity have severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy ).