Journal Article

Prolonged Production of NADPH Oxidase-Corrected Granulocytes after Gene Therapy of Chronic Granulomatous Disease

Fei Li, Charles S. Carter, Thomas A. Fleisher, Narda Whiting-Theobald, Sarah J. Vowells, Elizabeth J. Read, Harry L. Malech, Richard D. Schneiderman, Lawrence K. Cohen, Joseph A. Rokovich, Dennis E. Van Epps, Robert E. Butz, S. Kaye Spratt, Sudhir Sekhsaria, Phillip B. Maples, Gilda F. Linton, Christopher A. Maack, Judi A. Miller, John I. Gallin, Susan F. Leitman, Steven M. Holland, Ellen De Carlo

1997

Overview

Little is known about the potential for engraftment of autologous hematopoietic stem cells in human adults not subjected to myeloablative conditioning regimens. Five adult patients with the p47phoxdeficiency form of chronic granulomatous disease received intravenous infusions of autologous CD34+peripheral blood stem cells (PBSCs) that had been transduced ex vivo with a recombinant retrovirus encoding normal p47phox. Although marrow conditioning was not given, functionally corrected granulocytes were detectable in peripheral blood of all five patients. Peak correction occurred 3-6 weeks after infusion and ranged from 0.004 to 0.05% of total peripheral blood granulocytes. Corrected cells were detectable for as long as 6 months after infusion in some individuals. Thus, prolonged engraftment of autologous PBSCs and continued expression of the transduced gene can occur in adults without conditioning. This trial also piloted the use of animal protein-free medium and a blood-bank-compatible closed system of gas-permeable plastic containers for culture and transduction of the PBSCs. These features enhance the safety of PBSCs directed gene therapy.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences,The National Academy of Sciences of the USA
• Subject: Adolescent / Adult / Antigens, CD34 / Biological Sciences / Blood / Blood cells / Blood Component Removal / Bone marrow / Cells / Cultured cells / Disease / Female / Flow Cytometry / Follow-Up Studies / Gene therapy / Genetic Therapy - methods / Granulocytes / Granulocytes - enzymology / Granulomatous Disease, Chronic - therapy / Hematopoietic Stem Cell Transplantation / Humans / Male / NADPH Oxidases - biosynthesis / Neutrophils / Oxidases / Phosphoproteins - deficiency / Phosphoproteins - genetics / Phosphoproteins - immunology / Retroviridae - genetics / Stem cells / Transduction, Genetic