Details

Autor(en) / Beteiligte

• De Ravin, Suk See
• Wu, Xiaolin
• Moir, Susan
• Anaya-O'Brien, Sandra
• Kwatemaa, Nana
• Littel, Patricia
• Theobald, Narda
• Choi, Uimook
• Su, Ling
• Marquesen, Martha
• Hilligoss, Dianne
• Lee, Janet
• Buckner, Clarissa M
• Zarember, Kol A
• O'Connor, Geraldine
• McVicar, Daniel
• Kuhns, Douglas
• Throm, Robert E
• Zhou, Sheng
• Notarangelo, Luigi D
• Hanson, I Celine
• Cowan, Mort J
• Kang, Elizabeth
• Hadigan, Coleen
• Meagher, Michael
• Gray, John T
• Sorrentino, Brian P
• Malech, Harry L
• Kardava, Lela

Titel

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

Ist Teil von

• Science translational medicine, 2016-04, Vol.8 (335), p.335ra57

Ort / Verlag

United States

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.