Lentiviral hematopoietic stem cell gene therapy in patients with wiskott-aldrich syndrome

Science

Volumn 341, Issue 6148, 2013, Pages

  Aiuti, Alessandro ^a,b,c   Biasco, Luca ^a   Scaramuzza, Samantha ^a   Ferrua, Francesca ^b,d   Cicalese, Maria Pia ^b   Baricordi, Cristina ^a   Dionisio, Francesca ^a   Calabria, Andrea ^a   Giannelli, Stefania ^a   Castiello, Maria Carmina ^a,d   Bosticardo, Marita ^a   Evangelio, Costanza ^b   Assanelli, Andrea ^b   Casiraghi, Miriam ^b   Di Nunzio, Sara ^b   Callegaro, Luciano ^b   Benati, Claudia ^e   Rizzardi, Paolo ^e   Pellin, Danilo ^d   Di Serio, Clelia ^d   Schmidt, Manfred ^f   Von Kalle, Christof ^f   Gardner, Jason ^g   Mehta, Nalini ^h   Neduva, Victor ^h   Dow, David J ^h   Galy, Anne ⁱ   Miniero, Roberto ^j   Finocchi, Andrea ^c   Metin, Ayse ^k   Banerjee, Pinaki P ^l   Orange, Jordan S ^l   Galimberti, Stefania ^m   Valsecchi, Maria Grazia ^m   Biffi, Alessandra ^a,b   Montini, Eugenio ^a   Villa, Anna ^a,n   Ciceri, Fabio ^b   Roncarolo, Maria Grazia ^a,b,d   Naldini, Luigi ^a,d   more..

^a SAN RAFFAELE SCIENTIFIC INSTITUTE   (Italy)

^b SAN RAFFAELE HOSPITAL   (Italy)

^c BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^d VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^e MOLMED S P A   (Italy)

^f GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^g GLAXOSMITHKLINE   (United States)

^h GLAXOSMITHKLINE   (United Kingdom)

ⁱ Nationales Zentrum für Tumorerkrankungen ^*  (France)

^j UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^k Cardiovascular Surgery   (Turkey)

^l BAYLOR COLLEGE OF MEDICINE   (United States)

^m UNIVERSITY OF MILANO BICOCCA   (Italy)

ⁿ Milan Unit   (Italy)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ANTIVIRUS AGENT; BUSULFAN; FLUDARABINE; LENTIVIRUS VECTOR; RITUXIMAB; WISKOTT ALDRICH SYNDROME PROTEIN;

DISEASE; GENE; GENETIC ENGINEERING; MUTATION; PROTEIN; STEM;

AREA UNDER THE CURVE; ARTICLE; BACTERIAL INFECTION; BLOOD CELL; BONE MARROW CELL; CASE REPORT; CD34 SELECTION; CELL LINEAGE; CELL PROLIFERATION; CHILD; ECZEMA; GENE THERAPY; GENE TRANSFER; GRAFT REJECTION; HEMATOPOIETIC STEM CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFECTION PREVENTION; LYMPHOID CELL; MALE; MYCOSIS; MYELOABLATIVE CONDITIONING; PNEUMOCYSTOSIS; PRESCHOOL CHILD; PRIORITY JOURNAL; PROPHYLAXIS; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SINGLE DRUG DOSE; THROMBOCYTE COUNT; TREATMENT OUTCOME; VIRUS INFECTION; WISKOTT ALDRICH SYNDROME; GENE VECTOR; GENETIC TRANSDUCTION; GENETICS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; LENTIVIRINAE; METABOLISM; METHODOLOGY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; VIRUS DNA CELL DNA INTERACTION;

CHILD; GENETIC THERAPY; GENETIC VECTORS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMATOPOIETIC STEM CELLS; HUMANS; LENTIVIRUS; MALE; TRANSDUCTION, GENETIC; VIRUS INTEGRATION; WISKOTT-ALDRICH SYNDROME; WISKOTT-ALDRICH SYNDROME PROTEIN;

EID: 84879867061     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1233151     Document Type: Article

References (62)

1. L. D. Notarangelo, C. H. Miao, H. D. Ochs, Wiskott-Aldrich syndrome. Curr. Opin. Hematol. 15, 30-36 (2008). doi: 10.1097/MOH.0b013e3282f30448; pmid: 18043243
2. M. Catucci, M. C. Castiello, F. Pala, M. Bosticardo, A. Villa, Autoimmunity in Wiskott-Aldrich syndrome: An unsolved enigma. Front. Immunol. 3, 209 (2012). doi: 10.3389/fimmu.2012.00209; pmid: 22826711
3. L. Dupré et al., Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction. Mol. Ther. 10, 903-915 (2004). doi: 10.1016/j.ymthe.2004.08.008; pmid: 15509508
4. M. Bosticardo, F. Marangoni, A. Aiuti, A. Villa, M. Grazia Roncarolo, Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood 113, 6288-6295 (2009). doi: 10.1182/blood-2008-12-115253; pmid: 19351959
5. H. D. Ochs, A. H. Filipovich, P. Veys, M. J. Cowan, N. Kapoor, Wiskott-Aldrich syndrome: Diagnosis, clinical and laboratory manifestations, and treatment. Biol. Blood Marrow Transplant. 15 (suppl.), 84-90 (2009). doi: 10.1016/j.bbmt.2008.10.007; pmid: 19147084
6. H. Ozsahin et al., Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: Collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood 111, 439-445 (2008). doi: 10.1182/blood-2007-03-076679; pmid: 17901250
7. D. Moratto et al., Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: An international collaborative study. Blood 118, 1675-1684 (2011). doi: 10.1182/blood-2010-11-319376; pmid: 21659547
8. C. R. Shin et al., Outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome. Bone Marrow Transplant. 47, 1428-1435 (2012). doi: 10.1038/bmt.2012.31; pmid: 22426750
9. A. Aiuti et al., Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N. Engl. J. Med. 360, 447-458 (2009). doi: 10.1056/NEJMoa0805817; pmid: 19179314
10. S. Hacein-Bey-Abina et al., Efficacy of gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 363, 355-364 (2010). doi: 10.1056/NEJMoa1000164; pmid: 20660403
11. H. B. Gaspar et al., Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency. Sci. Transl. Med. 3, 97ra79 (2011). doi: 10.1126/scitranslmed.3002715; pmid: 21865537
12. K. Boztug et al., Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N. Engl. J. Med. 363, 1918-1927 (2010). doi: 10.1056/NEJMoa1003548; pmid: 21067383
13. H. B. Gaspar et al., How I treat ADA deficiency. Blood 114, 3524-3532 (2009). doi: 10.1182/blood-2009-06-189209; pmid: 19638621
14. L. W. Seymour, A. J. Thrasher, Gene therapy matures in the clinic. Nat. Biotechnol. 30, 588-593 (2012). doi: 10.1038/nbt.2290; pmid: 22781675
15. F. Candotti et al., Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: Clinical comparison of retroviral vectors and treatment plans. Blood 120, 3635-3646 (2012). doi: 10.1182/blood-2012-02-400937; pmid: 22968453
16. A. Aiuti et al., Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296, 2410-2413 (2002). doi: 10.1126/science.1070104; pmid: 12089448
17. S. J. Howe et al., Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J. Clin. Invest. 118, 3143-3150 (2008). doi: 10.1172/JCI35798; pmid: 18688286
18. S. Hacein-Bey-Abina et al., Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J. Clin. Invest. 118, 3132-3142 (2008). doi: 10.1172/JCI35700; pmid: 18688285
19. S. Stein et al., Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat. Med. 16, 198-204 (2010). doi: 10.1038/nm.2088; pmid: 20098431
20. M. Cavazzana-Calvo, A. Fischer, S. Hacein-Bey-Abina, A. Aiuti, Gene therapy for primary immunodeficiencies: Part 1. Curr. Opin. Immunol. 24, 580-584 (2012). doi: 10.1016/j.coi.2012.08.008; pmid: 22981681
21. G. P. Wang et al., Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial. Blood 115, 4356-4366 (2010). doi: 10.1182/blood-2009-12-257352; pmid: 20228274
22. A. Deichmann et al., Insertion sites in engrafted cells cluster within a limited repertoire of genomic areas after gammaretroviral vector gene therapy. Mol. Ther. 19, 2031-2039 (2011). doi: 10.1038/mt.2011.178; pmid: 21862999
23. L. Biasco, C. Baricordi, A. Aiuti, Retroviral integrations in gene therapy trials. Mol. Ther. 20, 709-716 (2012). doi: 10.1038/mt.2011.289; pmid: 22252453
24. J. Corrigan-Curay et al., Challenges in vector and trial design using retroviral vectors for long-term gene correction in hematopoietic stem cell gene therapy. Mol. Ther. 20, 1084-1094 (2012). doi: 10.1038/mt.2012.93; pmid: 22652996
25. L. Naldini, Ex vivo gene transfer and correction for cell-based therapies. Nat. Rev. Genet. 12, 301-315 (2011). doi: 10.1038/nrg2985; pmid: 21445084
26. E. Montini et al., Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat. Biotechnol. 24, 687-696 (2006). doi: 10.1038/nbt1216; pmid: 16732270
27. N. Cartier et al., Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326, 818-823 (2009). doi: 10.1126/science.1171242; pmid: 19892975
28. M. Cavazzana-Calvo et al., Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 467, 318-322 (2010). doi: 10.1038/nature09328; pmid: 20844535
29. C. Bartholomae, Assessing the integration profile of lentiviral vectors in gene therapy for X-adrenoleukodystrophy. Hum. Gene Ther. 23, A3 (2012) (abstract).
30. L. Dupré et al., Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation. Hum. Gene Ther. 17, 303-313 (2006). doi: 10.1089/hum.2006.17.303; pmid: 16544979
31. S. Charrier et al., Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients. Gene Ther. 14, 415-428 (2007). doi: 10.1038/sj.gt.3302863; pmid: 17051251
32. F. Marangoni et al., WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells. J. Exp. Med. 204, 369-380 (2007). doi: 10.1084/jem.20061334; pmid: 17296785
33. M. Bosticardo et al., Lentiviral-mediated gene therapy leads to improvement of B-cell functionality in a murine model of Wiskott-Aldrich syndrome. J. Allergy Clin. Immunol. 127, 1376, e5 (2011). doi: 10.1016/j.jaci.2011.03.030; pmid: 21531013
34. S. Scaramuzza et al., Preclinical safety and efficacy of human CD34(+) cells transduced with lentiviral vector for the treatment of Wiskott-Aldrich syndrome. Mol. Ther. 21, 175-184 (2013).pmid: 22371846
35. E. Montini et al., The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J. Clin. Invest. 119, 964-975 (2009). doi: 10.1172/JCI37630; pmid: 19307726
36. U. Modlich et al., Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol. Ther. 17, 1919-1928 (2009). doi: 10.1038/mt.2009.179; pmid: 19672245
37. F. Marangoni et al., Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models. Mol. Ther. 17, 1073-1082 (2009). doi: 10.1038/mt.2009.31; pmid: 19259069
38. A. Aiuti, R. Bacchetta, R. Seger, A. Villa, M. Cavazzana-Calvo, Gene therapy for primary immunodeficiencies: Part 2. Curr. Opin. Immunol. 24, 585-591 (2012). doi: 10.1016/j.coi.2012.07.012; pmid: 22909900
39. Q. Zhu et al., Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype. Blood 90, 2680-2689 (1997). pmid: 9326235
40. + regulatory T cells. J. Exp. Med. 204, 381-391 (2007). doi: 10.1084/jem.20061338; pmid: 17296786
41. J. S. Orange et al., Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses. Proc. Natl. Acad. Sci. U.S.A. 99, 11351-11356 (2002). doi: 10.1073/pnas.162376099; pmid: 12177428
42. M. Schmidt et al., High-resolution insertion-site analysis by linear amplification-mediated PCR (LAM-PCR). Nat. Methods 4, 1051-1057 (2007). doi: 10.1038/nmeth1103; pmid: 18049469
43. A. Paruzynski et al., Genome-wide high-throughput integrome analyses by nrLAM-PCR and next-generation sequencing. Nat. Protoc. 5, 1379-1395 (2010). doi: 10.1038/nprot.2010.87; pmid: 20671722
44. A. Chao, An overview of closed capture-recapture models. J. Agric. Biol. Environ. Stat. 6, 158-175 (2001). doi: 10.1198/108571101750524670
45. L. Biasco et al., Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell. EMBO Mol. Med. 3, 89-101 (2011). doi: 10.1002/emmm.201000108; pmid: 21243617
46. G. P. Wang, A. Ciuffi, J. Leipzig, C. C. Berry, F. D. Bushman, HIV integration site selection: Analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res. 17, 1186-1194 (2007). doi: 10.1101/gr.6286907; pmid: 17545577
47. K. Cui et al., Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell 4, 80-93 (2009). doi: 10.1016/j.stem.2008.11.011; pmid: 19128795
48. C. Y. McLean et al., GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495-501 (2010). doi: 10.1038/nbt.1630; pmid: 20436461
49. U. Abel et al., Analyzing the number of common integration sites of viral vectors: New methods and computer programs. PLoS ONE 6, e24247 (2011). doi: 10.1371/journal.pone.0024247; pmid: 22022353
50. A. Biffi et al., Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood 117, 5332-5339 (2011). doi: 10.1182/blood-2010- 09-306761; pmid: 21403130
51. C. Cattoglio et al., Hot spots of retroviral integration in human CD34+ hematopoietic cells. Blood 110, 1770-1778 (2007). doi: 10.1182/blood-2007-01- 068759; pmid: 17507662
52. A. Biffi et al., Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341, 1233158 (2013); .doi: 10.1126/science. 1233158
53. L. S. Westerberg et al., Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function. Blood 119, 3966-3974 (2012). doi: 10.1182/blood-2010-09-308197; pmid: 22411869
54. A. Astrakhan et al., Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich syndrome. Blood 119, 4395-4407 (2012). doi: 10.1182/blood-2011- 03-340711; pmid: 22431569
55. L. V. Bystrykh, E. Verovskaya, E. Zwart, M. Broekhuis, G. de Haan, Counting stem cells: Methodological constraints. Nat. Methods 9, 567-574 (2012). doi: 10.1038/nmeth.2043; pmid: 22669654
56. C. Cattoglio et al., High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors. Blood 116, 5507-5517 (2010). doi: 10.1182/blood-2010-05-283523; pmid: 20864581
57. K. Yamaguchi et al., Mixed chimera status of 12 patients with Wiskott-Aldrich syndrome (WAS) after hematopoietic stem cell transplantation: Evaluation by flow cytometric analysis of intracellular WAS protein expression. Blood 100, 1208-1214 (2002). doi: 10.1182/blood-2002-01-0211; pmid: 12149199
58. T. Wada et al., Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings. J. Clin. Invest. 111, 1389-1397 (2003). pmid: 12727931
59. A. V. Sauer et al., Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood 119, 1428-1439 (2012). doi: 10.1182/blood-2011-07- 366781; pmid: 22184407
60. J. S. Orange et al., IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function. J. Clin. Invest. 121, 1535-1548 (2011). doi: 10.1172/JCI44862; pmid: 21383498
61. D. S. Heo et al., Evaluation of tetrazolium-based semiautomatic colorimetric assay for measurement of human antitumor cytotoxicity. Cancer Res. 50, 3681-3690 (1990). pmid: 2340518
62. S. Trifari et al., Defective Th1 cytokine gene transcription in CD4+ and CD8+ T cells from Wiskott-Aldrich syndrome patients. J. Immunol. 177, 7451-7461 (2006). pmid: 17082665