Current progress on gene therapy for primary immunodeficiencies

Gene Therapy

Volumn 20, Issue 10, 2013, Pages 963-969

  Zhang, L ^a   Thrasher, A J ^a   Gaspar, H B ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

adenosine deaminase; lentiviral vectors; primary immunodeficiencies

Indexed keywords

LENTIVIRUS VECTOR; RETROVIRUS VECTOR; VIRUS VECTOR;

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; CHRONIC GRANULOMATOUS DISEASE; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG SAFETY; EX VIVO GENE TRANSFER; GENE INSERTION; HUMAN; IMMUNE DEFICIENCY; MUTAGENESIS; MYELODYSPLASTIC SYNDROME; NONHUMAN; PRIORITY JOURNAL; REVIEW; SCID MOUSE; SEVERE COMBINED IMMUNODEFICIENCY; T CELL LEUKEMIA; TECHNOLOGY; TREATMENT OUTCOME; VIRAL GENE THERAPY; WISKOTT ALDRICH SYNDROME;

ANIMALS; CLINICAL TRIALS AS TOPIC; GENETIC THERAPY; GENETIC VECTORS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOLOGIC DEFICIENCY SYNDROMES; LENTIVIRUS; SEVERE COMBINED IMMUNODEFICIENCY; TRANSDUCTION, GENETIC; TRANSPLANTATION, AUTOLOGOUS;

EID: 84885615479     PISSN: 09697128     EISSN: 14765462     Source Type: Journal    
DOI: 10.1038/gt.2013.21     Document Type: Review

References (91)

1. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol 2010; 125(2 Suppl 2): S182-S194.
2. Antoine C, Muller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Lancet 2003; 361: 553-560.
3. Gaspar HB, Aiuti A, Porta F, Candotti F, Hershfield MS, Notarangelo LD. How I treat ADA deficiency. Blood 2009; 114: 3524-3532.
4. Bousso P, Wahn V, Douagi I, Horneff G, Pannetier C, Le Deist F et al. Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor. Proc Natl Acad Sci USA 2000; 97: 274-278.
5. Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 1995; 270: 475-480.
6. Gaspar HB, Cooray S, Gilmour KC, Parsley KL, Adams S, Howe SJ 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.
7. Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2010; 363: 355-364.
8. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302: 415-419.
9. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118: 3132-3142.
10. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest 2008; 118: 3143-3150.
11. Thrasher AJ, Hacein-Bey-Abina S, Gaspar HB, Blanche S, Davies EG, Parsley K et al. Failure of SCID-X1 gene therapy in older patients. Blood 2005; 105: 4255-4257.
12. Chinen J, Davis J, De Ravin SS, Hay BN, Hsu AP, Linton GF et al. Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency. Blood 2007; 110: 67-73.
13. Albuquerque W, Gaspar HB. Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency. J Pediatr 2004; 144: 278-280.
14. Vlajkovic SM, Housley GD, Thorne PR. Adenosine and the auditory system. Curr Neuropharmacol 2009; 7: 246-256.
15. Onodera M, Ariga T, Kawamura N, Kobayashi I, Ohtsu M, Yamada M et al. Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency. Blood 1998; 91: 30-36.
16. Kohn DB, Weinberg KI, Nolta JA, Heiss LN, Lenarsky C, Crooks GM et al. Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency. Nat Med 1995; 1: 1017-1023.
17. Bordignon C, Notarangelo LD, Nobili N, Ferrari G, Casorati G, Panina P et al. Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science 1995; 270: 470-475.
18. Hoogerbrugge PM, van Beusechem VW, Fischer A, Debree M, le Deist F, Perignon JL et al. Bone marrow gene transfer in three patients with adenosine deaminase deficiency. Gene Therapy 1996; 3: 179-183.
19. Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A et al. Correction of ADASCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 2002; 296: 2410-2413.
20. Aiuti A, Vai S, Mortellaro A, Casorati G, Ficara F, Andolfi G et al. Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement. Nat Med 2002; 8: 423-425.
21. Gaspar HB, Cooray S, Gilmour KC, Parsley KL, Zhang F, Adams S et al. Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction. Sci Transl Med 3: 97ra80.
22. Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med 2009; 360: 447-458.
23. Candotti F, Shaw KL, Muul L, Carbonaro D, Sokolic R, Choi C et al. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood 2012; 120: 3635-3646.
24. Grunebaum E, Chung CT, Dadi H, Kim P, Brigida I, Ferrua F et al. Purine metabolism, immune reconstitution, and abdominal adipose tumor after gene therapy for adenosine deaminase deficiency. J Allergy Clin Immunol 2011; 127: 1417-9 e3.
25. Heyworth PG, Cross AR, Curnutte JT. Chronic granulomatous disease. Curr Opin Immunol 2003; 578-584.
26. Dinauer MC, Gifford MA, Pech N, Li LL, Emshwiller P. Variable correction of host defense following gene transfer and bone marrow transplantation in murine X-linked chronic granulomatous disease. Blood 2001; 97: 3738-3745.
27. Woodman RC, Newburger PE, Anklesaria P, Erickson RW, Rae J, Cohen MS et al. A new X-linked variant of chronic granulomatous disease characterized by the existence of a normal clone of respiratory burst-competent phagocytic cells. Blood 1995; 85: 231-241.
28. Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S, Vowells SJ et al. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci USA 1997; 94: 12133-12138.
29. Goebel WS, Dinauer MC. Gene therapy for chronic granulomatous disease. Acta Haematol 2003; 110: 86-92.
30. Grez M, Reichenbach J, Schwable J, Seger R, Dinauer MC, Thrasher AJ. Gene therapy of chronic granulomatous disease: the engraftment dilemma. Mol Ther 2011; 19: 28-35.
31. Kang HJ, Bartholomae CC, Paruzynski A, Arens A, Kim S, Yu SS et al. Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. Mol Ther 2011; 19: 2092-2101.
32. Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med 2006; 12: 401-409.
33. Stein S, Ott MG, Schultze-Strasser S, Jauch A, Burwinkel B, Kinner A et al. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med 2010; 16: 198-204.
34. Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Diez IA, Dewey RA et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med 2010; 363: 1918-1927.
35. Avedillo Diez I, Zychlinski D, Coci EG, Galla M, Modlich U, Dewey RA et al. Development of novel efficient SIN vectors with improved safety features for Wiskott-Aldrich syndrome stem cell based gene therapy. Mol Pharm 2011; 8: 1525-1537.
36. Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996; 272: 263-267.
37. Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001; 7: 33-40.
38. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 1998; 72: 8463-8471.
39. Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM. Development of a selfinactivating lentivirus vector. J Virol 1998; 72: 8150-8157.
40. Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L et al. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 1998; 72: 9873-9880.
41. Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science 2003; 300: 1749-1751.
42. Felice B, Cattoglio C, Cittaro D, Testa A, Miccio A, Ferrari G et al. Transcription factor binding sites are genetic determinants of retroviral integration in the human genome. PLoS ONE 2009; 4: e4571.
43. Wang GP, Levine BL, Binder GK, Berry CC, Malani N, McGarrity G et al. Analysis of lentiviral vector integration in HIV study subjects receiving autologous infusions of gene modified CD4 T cells. Mol Ther 2009; 17: 844-850.
44. Modlich U, Bohne J, Schmidt M, von Kalle C, Knoss S, Schambach A et al. Cellculture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood 2006; 108: 2545-2553.
45. Modlich U, Navarro S, Zychlinski D, Maetzig T, Knoess S, Brugman MH et al. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol Ther 2009; 17: 1919-1928.
46. Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, Ranzani M 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 2009; 119: 964-975.
47. Montini E, Cesana D, Schmidt M, Sanvito F, Ponzoni M, Bartholomae C et al. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol 2006; 24: 687-696.
48. Kiem HP, Allen J, Trobridge G, Olson E, Keyser K, Peterson L et al. Foamy-virusmediated gene transfer to canine repopulating cells. Blood 2007; 109: 65-70.
49. Suerth JD, Maetzig T, Brugman MH, Heinz N, Appelt JU, Kaufmann KB et al. Alpharetroviral self-inactivating vectors: long-term transgene expression in murine hematopoietic cells and low genotoxicity. Mol Ther 2012; 20: 1022-1032.
50. Suerth JD, Maetzig T, Galla M, Baum C, Schambach A. Self-inactivating alpharetroviral vectors with a split-packaging design. J Virol 2010; 84: 6626-6635.
51. Pai SY, Notarangelo LD, Harris C, Cattaneo F, Wladkowski M, Armant M et al. Somatic gene therapy for X-linked severe combined immunodeficiency using a self-inactivating modified gammaretroviral vector results in an improved preclinical safety profile and early clinical efficacy in a human patient. Blood 2011; 118: 164.
52. Ginn SL, Liao SH, Dane AP, Hu M, Hyman J, Finnie JW et al. Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and gammac overexpression. Mol Ther 2010; 18: 965-976.
53. Greene MR, Lockey T, Mehta PK, Kim YS, Eldridge PW, Gray JT et al. Transduction of human CD34() repopulating cells with a self-inactivating lentiviral vector for SCID-X1 produced at clinical scale by a stable cell line. Hum Gene Ther Methods 2012; 23: 297-308.
54. Huston MW, van Til NP, Visser TP, Arshad S, Brugman MH, Cattoglio C et al. Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning. Mol Ther 2011; 19: 1867-1877.
55. Astrakhan A, Sather BD, Ryu BY, Khim S, Singh S, Humblet-Baron S et al. Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich syndrome. Blood 2012; 119: 4395-4407.
56. Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S et al. Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models. Mol Ther 2009; 17: 1073-1082.
57. Scaramuzza S, Biasco L, Ripamonti A, Castiello MC, Loperfido M, Draghici E et al. Preclinical safety and efficacy of human CD34() cells transduced with lentiviral vector for the treatment of Wiskott-Aldrich syndrome. Mol Ther 2013; 21: 175-184.
58. Santilli G, Almarza E, Brendel C, Choi U, Beilin C, Blundell MP et al. Biochemical correction of X-CGD by a novel chimeric promoter regulating high levels of transgene expression in myeloid cells. Mol Ther 2011; 19: 122-132.
59. Cartier N, Hacein-Bey-Abina S, Von Kalle C, Bougneres P, Fischer A, Cavazzana-Calvo M et al. [Gene therapy of X-linked adrenoleukodystrophy using hematopoietic stem cells and a lentiviral vector]. Bull Acad Natl Med 2010; 194: 255-264, Discussion 264-268.
60. Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F et al. Transfusion independence and HMGA2 activation after gene therapy of human betathalassaemia. Nature 2010; 467: 318-322.
61. Pike-Overzet K, Rodijk M, Ng YY, Baert MR, Lagresle-Peyrou C, Schambach A et al. Correction of murine Rag1 deficiency by self-inactivating lentiviral vectormediated gene transfer. Leukemia 2011; 25: 1471-1483.
62. van Til NP, de Boer H, Mashamba N, Wabik A, Huston M, Visser TP et al. Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene. Mol Ther 2012; 20: 1968-1980.
63. Benjelloun F, Garrigue A, Demerens-de Chappedelaine C, Soulas-Sprauel P, Malassis-Seris M, Stockholm D et al. Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells. Mol Ther 2008; 16: 1490-1499.
64. Multhaup MM, Gurram S, Podetz-Pedersen KM, Karlen AD, Swanson DL, Somia NV et al. Characterization of the human artemis promoter by heterologous gene expression in vitro and in vivo. DNA Cell Biol 2011; 30: 751-761.
65. Bauer Jr. TR, Hickstein DD. Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther 2000; 2: 383-388.
66. Hunter MJ, Tuschong LM, Fowler CJ, Bauer Jr. TR, Burkholder TH, Hickstein DD. Gene therapy of canine leukocyte adhesion deficiency using lentiviral vectors with human CD11b and CD18 promoters driving canine CD18 expression. Mol Ther 2011; 19: 113-121.
67. Hunter MJ, Zhao H, Tuschong LM, Bauer Jr. TR, Burkholder TH, Persons DA et al. Gene therapy for canine leukocyte adhesion deficiency with lentiviral vectors using the murine stem cell virus and human phosphoglycerate kinase promoters. Hum Gene Ther 2011; 22: 689-696.
68. Bauer Jr. TR, Olson EM, Huo Y, Tuschong LM, Allen JM, Li Y et al. Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter. Gene Therapy 2011; 18: 553-559.
69. McCauslin CS, Wine J, Cheng L, Klarmann KD, Candotti F, Clausen PA et al. In vivo retroviral gene transfer by direct intrafemoral injection results in correction of the SCID phenotype in Jak3 knock-out animals. Blood 2003; 102: 843-848.
70. Rivat C, Booth C, Alonso-Ferrero M, Blundell M, Sebire NJ, Thrasher AJ et al. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease. Blood 2013; 121: 1073-1076.
71. Mortellaro A, Hernandez RJ, Guerrini MM, Carlucci F, Tabucchi A, Ponzoni M et al. Ex vivo gene therapy with lentiviral vectors rescues adenosine deaminase (ADA)-deficient mice and corrects their immune and metabolic defects. Blood 2006; 108: 2979-2988.
72. Toscano MG, Frecha C, Benabdellah K, Cobo M, Blundell M, Thrasher AJ et al. Hematopoietic-specific lentiviral vectors circumvent cellular toxicity due to ectopic expression of Wiskott-Aldrich syndrome protein. Hum Gene Ther 2008; 19: 179-197.
73. Almarza E, Zhang F, Santilli G, Blundell MP, Howe SJ, Thornhill SI et al. Correction of SCID-X1 using an enhancerless Vav promoter. Hum Gene Ther 2011; 22: 263-270.
74. Zhang F, Frost AR, Blundell MP, Bales O, Antoniou MN, Thrasher AJ. A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylationmediated silencing of lentiviral vectors. Mol Ther 2010; 18: 1640-1649.
75. Zhang F, Thornhill SI, Howe SJ, Ulaganathan M, Schambach A, Sinclair J et al. Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells. Blood 2007; 110: 1448-1457.
76. Sokolic R, Maric I, Kesserwan C, Garabedian E, Hanson IC, Dodds M et al. Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency. Blood 2011; 118: 2688-2694.
77. Bartelink IH, Boelens JJ, Bredius RG, Egberts AC, Wang C, Bierings MB et al. Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic stem cell transplantation patients: towards individualized dosing. Clin Pharmacokinet 2012; 51: 331-345.
78. Uchida N, Hsieh MM, Hayakawa J, Madison C, Washington KN, Tisdale JF. Optimal conditions for lentiviral transduction of engrafting human CD34 cells. Gene Therapy 2011; 18: 1078-1086.
79. Maetzig T, Brugman MH, Bartels S, Heinz N, Kustikova OS, Modlich U et al. Polyclonal fluctuation of lentiviral vector-transduced and expanded murine hematopoietic stem cells. Blood 2011; 117: 3053-3064.
80. Pessach IM, Notarangelo LD. Gene therapy for primary immunodeficiencies: looking ahead, toward gene correction. J Allergy Clin Immunol 2011; 127: 1344-1350.
81. Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA 1996; 93: 1156-1160.
82. Bibikova M, Beumer K, Trautman JK, Carroll D. Enhancing gene targeting with designed zinc finger nucleases. Science 2003; 300: 764.
83. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 2005; 435: 646-651.
84. Wu LC, Sun CW, Ryan TM, Pawlik KM, Ren J, Townes TM. Correction of sickle cell disease by homologous recombination in embryonic stem cells. Blood 2006; 108: 1183-1188.
85. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007; 318: 1920-1923.
86. Bedell VM, Wang Y, Campbell JM, Poshusta TL, Starker CG, Krug 2nd RG et al. In vivo genome editing using a high-efficiency TALEN system. Nature 2012; 491: 114-118.
87. Reyon D, Tsai SQ, Khayter C, Foden JA, Sander JD, Joung JK. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 2012; 30: 460-465.
88. Silva G, Poirot L, Galetto R, Smith J, Montoya G, Duchateau P et al. Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy. Curr Gene Ther 2011; 11: 11-27.
89. Kang EM, Choi U, Theobald N, Linton G, Long Priel DA, Kuhns D et al. Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. Blood 2010; 115: 783-791.
90. Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol 2011; 127: 1243-1252e7.
91. Rivat C, Santilli G, Gaspar HB, Thrasher AJ. Gene therapy for primary immunodeficiencies. Hum Gene Ther 2012; 23: 668-675.