30. Phase II Clinical Trial of Gene Therapy for Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID) Using a γ-Retroviral Vector

We report follow-up of subjects treated in a Phase II study of gene therapy for ADA-SCID. Between 2009 and 2012, ten ADA-deficient SCID patients were treated by γ-retroviral-mediated gene transfer (MND-ADA) to their bone marrow CD34+ cells. The subjects were given non-myeloablative chemotherapy (busulfan @ 90 mg/m2) and were withdrawn from PEG-ADA enzyme replacement therapy (ERT) prior to infusion of autologous gene-modified cells. Subject age at the time of treatment ranged from 3 months to 15 years (median = 11.5 months). Follow-up times range from 2 to 5 years. All but one subject, who was 15-years old at the time of treatment, remain off PEG-ADA ERT with immune reconstitution that reached maximal level between 6 and 12 months after transplant and was maintained thereafter. Vector marking in peripheral blood cells remained consistently detectable (> 0.1 copy/PBMC and ≥ 0.003 copy/granulocyte) at 2 years and later after transplant in subjects who discontinued ERT. These subjects also had PBMC ADA enzymatic activity in the normal range and red blood cell deoxynucleotide levels below 10%. Three subjects have discontinued intravenous immunoglobulin; five subjects have discontinued prophylactic antibiotics. All subjects have polyclonal gene marking with no sign of lymphoproliferative disease. The subjects remain in good health without infections or other complications.