Retroviral Gene Therapy for X-linked Chronic Granulomatous Disease: Results From Phase I/II Trial

摘要: X-linked chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by a defect in the gp91phox gene. In effort to treat X-CGD, we investigated safety and efficacy of gene therapy using retroviral vector, MT-gp91. Two X-CGD patients received autologous CD34+ cells transduced with MT-gp91 after conditioning regimen consisting fludarabine busulfan. The level gene-marked was highest at day 21 (8.3 11.7% peripheral blood cells) but decreased 0.08 0.5%, respectively, 3 years transfer. functionally corrected cells, as determined nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, reached peak 17 (6.5% patient 1 (P1) 14.3% 2 (P2) total granulocytes) declined 0.05% 0.21% (P2), later. Some vectors were found have integrated within or close proto-oncogenes MDS1-EVI1, PRDM16, CCND2; however, no abnormal cell expansion related hematological malignancy observed. Overall, transfer procedure did not produce any serious adverse effects able convert significant fraction biologically functional albeit for short period time.