Gene therapy of primary T cell immunodeficiencies

Abstract

Gene therapy of severe combined immunodeficiencies has been proven to be effective to provide sustained correction of the T cell immunodeficiencies. This has been achieved for 2 forms of SCID, i.e SCID-X1 (γc deficiency) and adenosine deaminase deficiency. Occurrence of gene toxicity generated by integration of first generation retroviral vectors, as observed in the SCID-X1 trials has led to replace these vectors by self inactivated (SIN) retro(or lenti) viruses that may provide equivalent efficacy with a better safety profile. Results of ongoing clinical studies in SCID as well as in other primary immunodeficiencies, such as the Wiskott Aldrich syndrome, will be thus very informative.

Keywords: ADA; GVHD; Gene therapy; HSC; HSCT; IPS; LV; Lentivirus; PIDs; RV; Retrovirus; SAE; SCID; SIN; Severe combined immune deficiencies; WAS; Wiskott Aldrich syndrome; Wiskott–Aldrich syndrome; adenosine deaminase; graft versus host disease; hematopoietic stem cell; hematopoietic stem cell transplantation; induced pluripotent cells; primary immunodeficiencies; retrovirus; self inactivated; serious adverse event; severe combined immunodeficiency.