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Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency
De Ravin, Suk S. Wu, Xiaolin Moir, Susan Anaya-O'Brien, Sandra Kwatemaa, Nana Littel, Patricia Theobald, Narda Choi, Uimook Su, Ling Marquesen, Martha
De Ravin, Suk S.
Wu, Xiaolin
Moir, Susan
Anaya-O'Brien, Sandra
Kwatemaa, Nana
Littel, Patricia
Theobald, Narda
Choi, Uimook
Su, Ling
Marquesen, Martha
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2016-04-20
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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 (gammac) of several interleukin receptors. Gamma-retroviral (gammaRV) 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 gammac 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.
Citation
De Ravin, S. S., et. al. (2016). Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Science Translational Medicine, 8(335), 335ra357. DOI:10.1126/scitranslmed.aad8856
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American Association for the Advancement of Science
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Science Translational Medicine
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Article
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en
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This document is the Accepted Manuscript version of a published work that appeared in final form in Science Translational Medicine. To access the final edited and published work see http://dx.doi.org/10.1126/scitranslmed.aad8856
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1946-6242