Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency
Year: 2016
Type: article
Abstract: X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.
Source: Science Translational Medicine
Authors: Suk See De Ravin, Xiaolin Wu, Susan Moir, Lela Kardava, Sandra Anaya-O’Brien, Nana Kwatemaa, Patricia Littel, Narda Theobald, Uimook Choi, Ling Su, Martha Marquesen, Dianne Hilligoss, Janet Lee, Clarissa M. Buckner, Kol A. Zarember, Geraldine O’Connor, Daniel McVicar, Douglas Kuhns, Robert E. Throm, Sheng Zhou, Luigi D. Notarangelo, I. Celine Hanson, Mort J. Cowan, Elizabeth Kang, Coleen Hadigan, Michael Meagher, John T. Gray, Brian P. Sorrentino, Harry L. Malech
Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), National Cancer Institute, St. Jude Children's Research Hospital, Boston Children's Hospital, Harvard University, Texas Children's Hospital, University of California, San Francisco, Audentes Therapeutics (United States)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G130109537, Primary Immune Deficiency Treatment Consortium, G3503792436, G386607036, G3915808128, G4460976858, G5888954722, G62655803, Clinical Diagnostic Studies and Treatment of Patients with Immune Deficiencies, G8937021053, G9000014658, Annual Primary Immune Deficiency Treatment Consortium (PIDTC) Workshop and Education Day
OpenAlex ID: W2341474073