Seminars in Hematology
Volume 41, Issue 4 , Pages 272-278 , October 2004

Gene therapy for immunodeficiency diseases

  • Alain Fischer

      Affiliations

    • INSERM U 429, Hôpital Necker-Enfants Malades, Paris, France
    • Corresponding Author InformationAddress correspondence to Alain Fischer, MD, INSERM U 429, Hôpital Necker-Enfants Malades, 149 rue de Sèvres-75015 Paris, France
    • ,
  • Salima Hacein-Bey-Abina

      Affiliations

    • INSERM U 429, Hôpital Necker-Enfants Malades, Paris, France
    • ,
  • Marina Cavazzana-Calvo

      Affiliations

    • INSERM U 429, Hôpital Necker-Enfants Malades, Paris, France

References 

  1. Cavazzana-Calvo M , Hacein-Bey S , de Saint Basile G , Gross F , Yvon E , Nusbaum P , et al.   Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease . Science . 2000;288:669–672
  2. Hacein-Bey-Abina S , Le Deist F , Carlier F , Bouneaud C , Hue C , De Villartay JP , et al.   Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy . N Engl J Med . 2002;346:1185–1193
  3. Aiuti A , Slavin S , Aker M , Ficara F , Deola S , Mortellaro A , et al.   Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning . Science . 2002;296:2410–2413
  4. Howe S , Thrasher AJ . Gene therapy for inherited immunodeficiencies . Curr Hematol Rep . 2003;2:328–334
  5. 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
  6. Fischer A . Primary immunodeficiency diseases (An experimental model for molecular medicine) . Lancet . 2001;357:1863–1869
  7. Buckley RH , Schiff SE , Schiff RI , Markert L , Williams LW , Roberts JL , et al.   Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency . N Engl J Med . 1999;340:508–516
  8. 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
  9. Patel DD , Gooding ME , Parrott RE , Curtis KM , Haynes BF , Buckley RH . Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency . N Engl J Med . 2000;342:1325–1332
  10. Fischer A , Hacein-Bey S , Cavazzana-Calvo M . Gene therapy of severe combined immunodeficiencies . Nat Rev Immunol . 2002;2:615
  11. Spits H . Development of alphabeta T cells in the human thymus . Nat Rev Immunol . 2002;2:760–772
  12. Hirschhorn R , Yang DR , Puck JM , Huie ML , Jiang CK , Kurlandsky LE . Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency . Nat Genet . 1996;13:290–295
  13. Ariga T , Oda N , Yamaguchi K , Kawamura N , Kikuta H , Taniuchi S , et al.   T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation . Blood . 2001;97:2896–2899
  14. Stephan V , Wahn V , Le Deist F , Dirksen U , Broker B , Muller-Fleckenstein I , et al.   Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells . N Engl J Med . 1996;335:1563–1567
  15. 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
  16. Wada T , Schurman SH , Otsu M , Garabedian EK , Ochs HD , Nelson DL , et al.   Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism . Proc Natl Acad Sci USA . 2001;98:8697–8702
  17. Wada T , Konno A , Schurman SH , Garabedian EK , Anderson SM , Kirby M , et al.   Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings . J Clin Invest . 2003;111:1389–1397
  18. Konno A , Wada T , Schurman SH , Garabedian EK , Kirby M , Anderson SM , et al.   Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineages . Blood . 2004;103:676–678
  19. Hirschhorn R . In vivo reversion to normal of inherited mutations in humans . J Med Genet . 2003;40:721–728
  20. Arredondo-Vega FX , Santisteban I , Richard E , Bali P , Koleilat M , Loubser M , et al.   Adenosine deaminase deficiency with mosaicism for a “second-site suppressor” of a splicing mutation (decline in revertant T lymphocytes during enzyme replacement therapy) . Blood . 2002;99:1005–1013
  21. Villard J , Masternak K , Lisowska-Grospierre B , Fischer A , Reith W . MHC class II deficiency (A disease of gene regulation) . Medicine (Baltimore) . 2001;80:405–418
  22. Boxer L , Dale DC . Neutropenia (Causes and consequences) . Semin Hematol . 2002;39:75–81
  23. Segal BH , Leto TL , Gallin JI , Malech HL , Holland SM . Genetic, biochemical, and clinical features of chronic granulomatous disease . Medicine (Baltimore) . 2000;79:170–200
  24. Wehrle-Haller B , Imhof BA . Integrin-dependent pathologies . J Pathol . 2003;200:481–487
  25. 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
  26. Bauer TR , Schwartz BR , Liles WC , Ochs HD , Hickstein DD . Retroviral-mediated gene transfer of the leukocyte integrin CD18 into peripheral blood CD34+ cells derived from a patient with leukocyte adhesion deficiency type 1 . Blood . 1998;91:1520–1526
  27. Riviere I , Brose K , Mulligan RC . Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells . Proc Natl Acad Sci USA . 1995;92:6733–6737
  28. 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
  29. Muul LM , Tuschong LM , Soenen SL , Jagadeesh GJ , Ramsey WJ , Long Z , et al.   Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components (Long-term results of the first clinical gene therapy trial) . Blood . 2003;101:2563–2569
  30. Schmidt M , Carbonaro DA , Speckmann C , Wissler M , Bohnsack J , Elder M , et al.   Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates . Nat Med . 2003;9:463–468
  31. 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
  32. Halene S , Wang L , Cooper RM , Bockstoce DC , Robbins PB , Kohn DB . Improved expression in hematopoietic and lymphoid cells in mice after transplantation of bone marrow transduced with a modified retroviral vector . Blood . 1999;94:3349–3357
  33. McKenna HJ , de Vries P , Brasel K , Lyman SD , Williams DE . Effect of flt3 ligand on the ex vivo expansion of human CD34+ hematopoietic progenitor cells . Blood . 1995;86:3413–3420
  34. Luens KM , Travis MA , Chen BP , Hill BL , Scollay R , Murray LJ . Thrombopoietin, kit ligand, and flk2/flt3 ligand together induce increased numbers of primitive hematopoietic progenitors from human CD34+Thy-1+Lin− cells with preserved ability to engraft SCID-hu bone . Blood . 1998;91:1206–1215
  35. Murray LJ , Young JC , Osborne LJ , Luens KM , Scollay R , Hill BL . Thrombopoietin, flt3, and kit ligands together suppress apoptosis of human mobilized CD34+ cells and recruit primitive CD34+ Thy-1+ cells into rapid division . Exp Hematol . 1999;27:1019–1028
  36. Hanenberg H , Xiao XL , Dilloo D , Hashino K , Kato I , Williams DA . Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cells . Nat Med . 1996;2:876–882
  37. Kiem HP , Heyward S , Winkler A , Potter J , Allen JM , Miller AD , et al.   Gene transfer into marrow repopulating cells (Comparison between amphotropic and gibbon ape leukemia virus pseudotyped retroviral vectors in a competitive repopulation assay in baboons) . Blood . 1997;90:4638–4645
  38. Kelly PF , Vandergriff J , Nathwani A , Nienhuis AW , Vanin EF . Highly efficient gene transfer into cord blood nonobese diabetic/severe combined immunodeficiency repopulating cells by oncoretroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein . Blood . 2000;96:1206–1214
  39. Dotti G , Savoldo B , Yotnda P , Rill D , Brenner MK . Transgenic expression of CD40 ligand produces an in vivo antitumor immune response against both CD40(+) and CD40(-) plasmacytoma cells . Blood . 2002;100:200–207
  40. Rieux-Laucat F , Le Deist F , Fischer A . Autoimmune lymphoproliferative syndromes (Genetic defects of apoptosis pathways) . Cell Death Differ . 2003;10:124–133
  41. Courtois G , Smahi A , Reichenbach J , Doffinger R , Cancrini C , Bonnet M , et al.   A hypermorphic I{kappa}B{alpha} mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency . J Clin Invest . 2003;112:1108–1115
  42. Candotti F , Johnston JA , Puck JM , Sugamura K , O’Shea JJ , Blaese RM . Retroviral-mediated gene correction for X-linked severe combined immunodeficiency . Blood . 1996;87:3097–3102
  43. 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
  44. Li Z, Dullmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J, et al  Murine leukemia induced by retroviral gene marking . Science . 2002;296:497
  45. Leonard WJ . Cytokines and immunodeficiency diseases . Nat Rev Immunol . 2001;1:200–208
  46. Lo M , Bloom ML , Imada K , Berg M , Bollenbacher JM , Bloom ET , et al.   Restoration of lymphoid populations in a murine model of X-linked severe combined immunodeficiency by a gene-therapy approach . Blood . 1999;94:3027–3036
  47. Soudais C , Tusjino S , Sharara LI , Guy-Grand D , Taniguchi T , Fischer A , et al.   Stable and functional lymphoid reconstitution common cytokine receptor gamma chain deficient mice by retroviral-mediated gene transfer . Blood . 2000;95:3071–3077
  48. Otsu M , Anderson SM , Bodine DM , Puck JM , O’Shea JJ , Candotti F . Lymphoid development and function in X-linked severe combined immunodeficiency mice after stem cell gene therapy . Mol Ther . 2000;1:145–153
  49. Otsu M , Sugamura K , Candotti F . Lack of dominant-negative effects of a truncated gammac on retroviral-mediated gene correction of immunodeficient mice . Blood . 2001;97:1618–1624
  50. Bunting KD , Flynn KJ , Riberdy JM , Doherty PC , Sorrentino BP . Virus-specific immunity after gene therapy in a murine model of severe combined immunodeficiency . Proc Natl Acad Sci USA . 1999;96:232–237
  51. Bunting KD , Lu T , Kelly PF , Sorrentino BP . Self-selection by genetically modified committed lymphocyte precursors reverses the phenotype of JAK3-deficient mice without myeloablation . Hum Gene Ther . 2000;11:2353–2364
  52. Tsai EJ , Malech HL , Kirby MR , Hsu AP , Seidel NE , Porada CD , et al.   Retroviral transduction of IL2RG into CD34(+) cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras . Blood . 2002;100:72–79
  53. Hacein-Bey S , Gross F , Nusbaum P , Hue C , Hamel Y , Fischer A , et al.   Optimization of retroviral gene transfer protocol to maintain the lymphoid potential of progenitor cells . Hum Gene Ther . 2001;12:291–301
  54. Schmidt M, Hacein-Bey-Abina S, Wissler M, Carlier F, Lim A, Prinz C, et al: Clonal evidence of hematopoietic stem cell transduction in the gene therapy trial for (SCID) X1. Submitted.
  55. Schmidt M , Zickler P , Hoffmann G , Haas S , Wissler M , Muessig A , et al.   Polyclonal long-term repopulating stem cell clones in a primate model . Blood . 2002;100:2737–2743
  56. Royer-Pokora B , Loos U , Ludwig WD . TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11) . Oncogene . 1991;6:1887–1893
  57. Neale GA , Rehg JE , Goorha RM . Ectopic expression of rhombotin-2 causes selective expansion of CD4−CD8− lymphocytes in the thymus and T-cell tumors in transgenic mice . Blood . 1995;86:3060–3071
  58. Li XC , Demirci G , Ferrari-Lacraz S , Groves C , Coyle A , Malek TR , et al.   IL-15 and IL-2 (A matter of life and death for T cells in vivo) . Nat Med . 2001;7:114–118
  59. Dave UP , Jenkins NA , Copeland NG . Gene therapy insertional mutagenesis insights . Science . 2004;303:333
  60. Hirose J , Kouro T , Igarashi H , Yokota T , Sakaguchi N , Kincade PW . A developing picture of lymphopoiesis in bone marrow . Immunol Rev . 2002;189:28–40
  61. Kohn DB , Sadelain M , Dunbar C , Bodine D , Kiem HP , Candotti F , et al.   American Society of Gene Therapy (ASGT) ad hoc subcommittee on retroviral-mediated gene transfer to hematopoietic stem cells . Mol Ther . 2003;8:180–187
  62. 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
  63. 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
  64. 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 Ther . 1996;3:179–183
  65. 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
  66. Aiuti A , Ficara F , Cattaneo F , Bordignon C , Roncarolo MG . Gene therapy for adenosine deaminase deficiency . Curr Opin Allergy Clin Immunol . 2003;3:461–466
  67. Yates F , Malassis-Seris M , Stockholm D , Bouneaud C , Larousserie F , Noguiez-Hellin P , et al.   Gene therapy of RAG-2−/− mice (Sustained correction of the immunodeficiency) . Blood . 2002;22:22
  68. Taylor N , Bacon KB , Smith S , Jahn T , Kadlecek TA , Uribe L , et al.   Reconstitution of T cell receptor signaling in ZAP-70-deficient cells by retroviral transduction of the ZAP-70 gene . J Exp Med . 1996;184:2031–2036
  69. Pacheco-Castro A , Martin-Fernandez JM , Millan R , Sanal O , Allende L , Regueiro JR . Toward gene therapy for human CD3 deficiencies . Hum Gene Ther . 2003;14:1653–1661
  70. Bradley MB , Fernandez JM , Ungers G , Diaz-Barrientos T , Steimle V , Mach B , et al.   Correction of defective expression in MHC class II deficiency (bare lymphocyte syndrome) cells by retroviral transduction of CIITA . J Immunol . 1997;159:1086–1095
  71. Imai K , Nonoyama S , Ochs HD . WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype . Curr Opin Allergy Clin Immunol . 2003;3:427–436
  72. Klein C , Nguyen D , Liu CH , Mizoguchi A , Bhan AK , Miki H , et al.   Gene therapy for Wiskott-Aldrich syndrome (Rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice) . Blood . 2003;101:2159–2166
  73. Dinauer MC , Li LL , Bjorgvinsdottir H , Ding C , Pech N . Long-term correction of phagocyte NADPH oxidase activity by retroviral-mediated gene transfer in murine X-linked chronic granulomatous disease . Blood . 1999;94:914–922
  74. Mardiney M , Jackson SH , Spratt SK , Li F , Holland SM , Malech HL . Enhanced host defense after gene transfer in the murine p47phox-deficient model of chronic granulomatous disease . Blood . 1997;89:2268–2275
  75. Bauer TR , Hickstein DD . Gene therapy for leukocyte adhesion deficiency . Curr Opin Mol Ther . 2000;2:383–388
  76. Malech HL . Use of serum-free medium with fibronectin fragment enhanced transduction in a system of gas permeable plastic containers to achieve high levels of retrovirus transduction at clinical scale . Stem Cells . 2000;18:155–156
  77. Brenner S , Whiting-Theobald NL , Linton GF , Holmes KL , Anderson-Cohen M , Kelly PF , et al.   Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/beta-microglobulin−/− repopulating mobilized human peripheral blood CD34+ cells . Blood . 2003;102:2789–2797
  78. Goebel WS , Dinauer MC . Gene therapy for chronic granulomatous disease . Acta Haematol . 2003;110:86–92
  79. Yanay O , Barry SC , Katen LJ , Brzezinski M , Flint LY , Christensen J , et al.   Treatment of canine cyclic neutropenia by lentivirus-mediated G-CSF delivery . Blood . 2003;102:2046–2052
  80. May C , Rivella S , Callegari J , Heller G , Gaensler KM , Luzzatto L , et al.   Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin . Nature . 2000;406:82–86
  81. Pawliuk R , Westerman KA , Fabry ME , Payen E , Tighe R , Bouhassira EE , et al.   Correction of sickle cell disease in transgenic mouse models by gene therapy . Science . 2001;294:2368–2371
  82. Recillas-Targa F , Pikaart MJ , Burgess-Beusse B , Bell AC , Litt MD , West AG , et al.   Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities . Proc Natl Acad Sci USA . 2002;99:6883–6888
  83. Olivares EC , Hollis RP , Chalberg TW , Meuse L , Kay MA , Calos MP . Site-specific genomic integration produces therapeutic factor IX levels in mice . Nat Biotechnol . 2002;20:1124–1128
  84. Porteus MH , Cathomen T , Weitzman MD , Baltimore D . Efficient gene targeting mediated by adeno-associated virus and DNA double-strand breaks . Mol Cell Biol . 2003;23:3558–3565
  85. Zennou V , Petit C , Guetard D , Nerhbass U , Montagnier L , Charneau P . HIV-1 genome nuclear import is mediated by a central DNA flap . Cell . 2000;101:173–185
  86. Krosl J , Austin P , Beslu N , Kroon E , Humphries RK , Sauvageau G . In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein . Nat Med . 2003;9:1428–1432
  87. Amsellem S , Pflumio F , Bardinet D , Izac B , Charneau P , Romeo PH , et al.   Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein . Nat Med . 2003;9:1423–1427
  88. Reya T , Duncan AW , Ailles L , Domen J , Scherer DC , Willert K , et al.   A role for Wnt signalling in self-renewal of haematopoietic stem cells . Nature . 2003;423:409–414

PII: S0037-1963(04)00126-X

doi: 10.1053/j.seminhematol.2004.07.003

Seminars in Hematology
Volume 41, Issue 4 , Pages 272-278 , October 2004

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