Lentiviral Gene Therapy for Artemis-Deficient SCID.

Autor:	Cowan MJ; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Yu J; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Facchino J; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Fraser-Browne C; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Sanford U; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Kawahara M; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Dara J; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Long-Boyle J; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Oh J; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Chan W; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Chag S; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Broderick L; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Chellapandian D; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Decaluwe H; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Golski C; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Hu D; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Kuo CY; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Miller HK; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Petrovic A; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Currier R; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Hilton JF; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Punwani D; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Dvorak CC; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Malech HL; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., McIvor RS; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.)., Puck JM; From the Departments of Pediatrics (M.J.C., J.Y., J.F., C.F.-B., U.S., M.K., J.D., J.L.-B., W.C., S.C., R.C., C.C.D., J.M.P.) and Epidemiology and Biostatistics (J.F.H.), the Smith Cardiovascular Research Institute (M.J.C., J.M.P.), and the School of Pharmacy (J.L.-B.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.J.C., J.F., J.D., J.L.-B., J.O., C.C.D., J.M.P.), San Francisco, the Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego (L.B.), and the Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles (C.Y.K.) - all in California; the Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL (D.C.); the Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal (H.D.); Tuba City Regional Health Care, Tuba City (C.G., D.H.), and Phoenix Children's Hospital, Phoenix (H.K.M.) - both in Arizona; the Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle (A.P.); Clinical Development, Roche Diagnostics Solutions, Singapore (D.P.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (H.L.M.); and the Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis (R.S.M.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2022 Dec 22; Vol. 387 (25), pp. 2344-2355.
DOI:	10.1056/NEJMoa2206575
Abstrakt:	Background: The DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in DCLRE1C , which encodes Artemis, cause Artemis-deficient severe combined immunodeficiency (ART-SCID), which is poorly responsive to allogeneic hematopoietic-cell transplantation. Methods: We carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing DCLRE1C , in 10 infants with newly diagnosed ART-SCID. We followed them for a median of 31.2 months. Results: Marrow harvest, busulfan conditioning, and lentiviral-transduced CD34+ cell infusion produced the expected grade 3 or 4 adverse events. All the procedures met prespecified criteria for feasibility at 42 days after infusion. Gene-marked T cells were detected at 6 to 16 weeks after infusion in all the patients. Five of 6 patients who were followed for at least 24 months had T-cell immune reconstitution at a median of 12 months. The diversity of T-cell receptor β chains normalized by 6 to 12 months. Four patients who were followed for at least 24 months had sufficient B-cell numbers, IgM concentration, or IgM isohemagglutinin titers to permit discontinuation of IgG infusions. Three of these 4 patients had normal immunization responses, and the fourth has started immunizations. Vector insertion sites showed no evidence of clonal expansion. One patient who presented with cytomegalovirus infection received a second infusion of gene-corrected cells to achieve T-cell immunity sufficient for viral clearance. Autoimmune hemolytic anemia developed in 4 patients 4 to 11 months after infusion; this condition resolved after reconstitution of T-cell immunity. All 10 patients were healthy at the time of this report. Conclusions: Infusion of lentiviral gene-corrected autologous CD34+ cells, preceded by pharmacologically targeted low-exposure busulfan, in infants with newly diagnosed ART-SCID resulted in genetically corrected and functional T and B cells. (Funded by the California Institute for Regenerative Medicine and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03538899.). (Copyright © 2022 Massachusetts Medical Society.)
Databáze:	MEDLINE
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