Gene Transfer for SCID-X1 Using a Self-inactivating Lentiviral Vector （TYF-IL-2Rg）

Gene Transfer for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self-inactivating Lentiviral Vector （TYF-IL-2Rg）

This is a Phase I/II clinical trial of gene transfer for treating X-linked severe combined immunodeficiency (SCID-X1) using a self-inactivating lentiviral vector TYF-IL-2Rg to functionally correct the defective gene(s). The primary objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.

X-linked severe combined immunodeficiency (SCID-X1) is a genetic disorder caused by defects in the common cytokine receptor chain, normally on the surface of lymphocytes. Individuals with SCID-X1 lack the normal development of a functional immune system and so have difficulty fighting infections, which may lead to chronic or severe illness and death. X-SCID patients are normally rescued by a bone marrow transplant from a healthy donor. This trial aims to treat SCID-X1 using a self-inactivating lentiviral vector carrying a functional gene to correct the genetic defect. By collecting an individual's stem cells and modifying them with a lentivirus, the gene-corrected cells can be returned into the blood to help produce normal healthy immune cells. The primary objectives are to evaluate the safety of the self-inactivating lentiviral vector TYF-IL-2Rg, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment, assessment of integration sites, and finally the long-term correction of immunodeficiency.

Inclusion Criteria: Diagnosis of classical SCID-X1 based on: A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA. T-cell immune deficiency defined as one or more of the following: CD3+ autologous T cells < 300/ul, or less than 50% of normal value for in vitro mitogen stimulation, or absent proliferation in vitro to antigens. With severe infections, including but not limited to: pneumonitis; protracted diarrhea requiring total parenteral nutrition; infection with herpes viruses or adenovirus or fungus; disseminated BCG infection. No cytogenetic abnormalities (medullary karyotype) and no detection of main rearrangements associated with acute leukemia of children. No prior allogeneic stem cell transplantation. Life expectancy ≥ 2 months. Negative for HIV infection. Written, informed consent obtained prior to any study-specific procedures. Exclusion Criteria: None