Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β -thalassemia and sickle cell disease

Current Gene Therapy

Volumn 15, Issue 1, 2015, Pages 64-81

  Negre, Olivier ^a,b,c   Bartholomae, Cynthia ^d   Beuzard, Yves ^a,b,c   Cavazzana, Marina ^e,f,g   Christiansen, Lauryn ^h   Courne, Céline ^a,b,c   Deichmann, Annette ^d   Denaro, Maria ^h   De Dreuzy, Edouard ^a,b   Finer, Mitchell ^h   Fronza, Raffaele ^d   Gillet Legrand, Béatrix ^a,b,c   Joubert, Christophe ^a   Kutner, Robert ^h   Leboulch, Philippe ^a,b,i   Maouche, Leïla ^a,b   Paulard, Anaïs ^a,b,c   Pierciey, Francis J ^h   Rothe, Michael ^j   Ryu, Byoung ^h   Schmidt, Manfred ^d   Von Kalle, Christof ^d   Payen, Emmanuel ^a,b   Veres, Gabor ^h   more..

^a INSTITUT DE RADIOPROTECTION ET DE SÛRETÉ NUCLÉAIRE   (France)

^b UNIVERSITÉ PARIS SACLAY   (France)

^c CEA   (France)

^d GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^e IMAGINE INSTITUTE   (France)

^f UNIVERSITÉ PARIS DESCARTES   (France)

^g ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^h BLUEBIRD BIO   (United States)

ⁱ BRIGHAM AND WOMEN S HOSPITAL   (United States)

^j HANNOVER MEDICAL SCHOOL   (Germany)

more..

Author keywords

Gene therapy; Lentiviral vector; Mouse model; hemoglobinopathy; thalassemia

Indexed keywords

BILIRUBIN; LENTIVIRUS VECTOR; CD34 ANTIGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPSY; BETA THALASSEMIA; BIOINFORMATICS; BONE MARROW TRANSPLANTATION; CONTROLLED STUDY; DIVERSITY INDEX; DRUG EFFICACY; DRUG SAFETY; FEMALE; FLOW CYTOMETRY; GENETIC TRANSDUCTION; GENOTOXICITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOHISTOCHEMISTRY; MALE; MEDICAL PARAMETERS; MOUSE; NONHUMAN; PHENOTYPE; POLYMERASE CHAIN REACTION; SICKLE CELL ANEMIA; YOUNG ADULT; ANEMIA, SICKLE CELL; ANIMAL; BETA-THALASSEMIA; BIOLOGY; C57BL MOUSE; DISEASE MODEL; DNA DAMAGE; GENE EXPRESSION; GENE THERAPY; GENE TRANSFER; GENE VECTOR; GENETICS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; LENTIVIRINAE; METABOLISM; PROCEDURES;

MUS;

ANEMIA, SICKLE CELL; ANIMALS; ANTIGENS, CD34; BETA-THALASSEMIA; COMPUTATIONAL BIOLOGY; DISEASE MODELS, ANIMAL; DNA DAMAGE; FEMALE; GENE EXPRESSION; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; LENTIVIRUS; MALE; MICE; MICE, INBRED C57BL;

EID: 84926339367     PISSN: 15665232     EISSN: 18755631     Source Type: Journal    
DOI: 10.2174/1566523214666141127095336     Document Type: Article

References (58)

1. [1] Cartier N, Hacein-Bey-Abina S, Bartholomae CC, et al. Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy. Method Enzymol 2012; 507: 187-98.
2. [2] Cartier N, Hacein-Bey-Abina S, Bartholomae CC, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in Xlinked adrenoleukodystrophy. Science 2009; 326: 818-23.
3. [3] Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 2010; 467: 318-22.
4. [4] Payen E, Leboulch P. Advances in stem cell transplantation and gene therapy in the beta-hemoglobinopathies. Hematology 2012; 2012: 276-83.
5. [5] Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 2013; 341: 1233158.
6. [6] Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 2013; 341: 1233151.
7. [7] Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis 2010; 5: 11.
8. [8] Isgro A, Gaziev J, Sodani P, et al. Progress in hematopoietic stem cell transplantation as allogeneic cellular gene therapy in thalassemia. Ann N Y Acad Sci 2010; 1202: 149-54.
9. [9] Lucarelli G, Galimberti M, Polchi P, et al. Marrow transplantation in patients with advanced thalassemia. New Eng J Med 1987; 316: 1050-5.
10. [10] Caocci G, Efficace F, Ciotti F, et al. Prospective assessment of health-related quality of life in pediatric patients with betathalassemia following hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17: 861-6.
11. [11] Luznik L, Jones RJ and Fuchs EJ. High-dose cyclophosphamide for graft-versus-host disease prevention. Curr Opin Hematol 2010; 17: 493-9.
12. [12] Borgna-Pignatti C. The life of patients with thalassemia major. Haematologica 2010; 95: 345-8.
13. [13] Modell B, Khan M, Darlison M, et al. Improved survival of thalassaemia major in the UK and relation to T2*. Cardiovasc Magn Reson 2008; 10: 42.
14. [14] Thuret I, Pondarre C, Loundou A, et al. Complications and treatment of patients with beta-thalassemia in France: results of the National Registry. Haematologica 2010; 95: 724-9.
15. [15] Bank A, Dorazio R, Leboulch P. A phase I/II clinical trial of betaglobin gene therapy for beta-thalassemia. Ann N Y Acad Sci 2005; 1054: 308-16.
16. [16] Recillas-Targa F, Pikaart MJ, Burgess-Beusse B, et al. Positioneffect protection and enhancer blocking by the chicken beta-globin insulator are separable activities. Proc Natl Acad Sci U S A 2002; 99: 6883-8.
17. [17] Bell AC, West AG, Felsenfeld G. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 1999; 98: 387-96.
18. [18] Ryu BY, Evans-Galea MV, Gray JT, et al. An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation. Blood 2008; 111: 1866-75.
19. [19] Desprat R and Bouhassira EE. Gene specificity of suppression of transgene-mediated insertional transcriptional activation by the chicken HS4 insulator. PloS One 2009; 4: e5956.
20. [20] Hanawa H, Yamamoto M, Zhao H, et al. Optimized lentiviral vector design improves titer and transgene expression of vectors containing the chicken beta-globin locus HS4 insulator element. Mol Ther 2009; 17: 667-74.
21. [21] Jakobsson J, Rosenqvist N, Thompson L, et al. Dynamics of transgene expression in a neural stem cell line transduced with lentiviral vectors incorporating the cHS4 insulator. Exp Cell Res 2004; 298: 611-23.
22. [22] Nielsen TT, Jakobsson J, Rosenqvist N, et al. Incorporating double copies of a chromatin insulator into lentiviral vectors results in less viral integrants. BMC Biotechnol 2009; 9: 13.
23. [23] Ronen K, Negre O, Roth S, et al. Distribution of lentiviral vector integration sites in mice following therapeutic gene transfer to treat beta-thalassemia. Mol Ther 2011; 19: 1273-86.
24. [24] Kutner RH, Puthli S, Marino MP, et al. Simplified production and concentration of HIV-1-based lentiviral vectors using HYPERFlask vessels and anion exchange membrane chromatography. BMC Biotechnol 2009; 9: 10.
25. [25] Kutner RH, Zhang XY, Reiser J. Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors. Nat Protoc 2009; 4: 495-505.
26. [26] Payen E, Colomb C, Negre O, et al. Lentivirus vectors in betathalassemia. Method Enzymol 2012; 507: 109-24.
27. [27] Modlich U, Navarro S, Zychlinski D, et al. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol Ther 2009; 17: 1919-28.
28. [28] Skow LC, Burkhart BA, Johnson FM, et al. A mouse model for beta-thalassemia. Cell 1983; 34: 1043-52.
29. [29] Rouyer-Fessard P, Leroy-Viard K, Domenget C, et al. Mouse beta thalassemia, a model for the membrane defects of erythrocytes in the human disease. J Biol Chem 1990; 265: 20247-51.
30. [30] Negre O, Fusil F, Colomb C, et al. Correction of murine betathalassemia after minimal lentiviral gene transfer and homeostatic in vivo erythroid expansion. Blood 2011; 117: 5321-31.
31. [31] Kittel B, Ruehl-Fehlert C, Morawietz G, et al. Revised guides for organ sampling and trimming in rats and mice--Part 2. A joint publication of the RITA and NACAD groups. Exp Toxicol Pathol 2004; 55: 413-31.
32. [32] Morawietz G, Ruehl-Fehlert C, Kittel B, et al. Revised guides for organ sampling and trimming in rats and mice--Part 3. A joint publication of the RITA and NACAD groups. Exp Toxicol Pathol 2004; 55: 433-49.
33. [33] Ruehl-Fehlert C, Kittel B, Morawietz G, et al. Revised guides for organ sampling and trimming in rats and mice--part 1. Exp Toxicol Pathol 2003; 55: 91-106.
34. [34] Paruzynski A, Arens A, Gabriel R, et al. Genome-wide highthroughput integrome analyses by nrLAM-PCR and nextgeneration sequencing. Nat Protoc 2010; 5: 1379-95.
35. [35] Schmidt M, Schwarzwaelder K, Bartholomae C, et al. Highresolution insertion-site analysis by linear amplification-mediated PCR (LAM-PCR). Nat Methods 2007; 4: 1051-7.
36. [36] Gabriel R, Eckenberg R, Paruzynski A, et al. Comprehensive genomic access to vector integration in clinical gene therapy. Nat Med 2009; 15: 1431-6.
37. [37] Arens A, Appelt JU, Bartholomae CC, et al. Bioinformatic clonality analysis of next-generation sequencing-derived viral vector integration sites. Hum Gene Ther Methods 2012; 23: 111-8.
38. [38] Abel U, Deichmann A, Nowrouzi A, et al. Analyzing the number of common integration sites of viral vectors--new methods and computer programs. PloS One 2011; 6: e24247.
39. [39] Modlich U, Bohne J, Schmidt M, et al. Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood 2006; 108: 2545-53.
40. [40] Negre O, Bartholoma C, Kutner R, et al. Abstract 674 of the American Society of Gene & Cell Therapy (ASGGT) 16th Annual Meeting. May 15-18, 2013. Salt Lake City, Utah, USA. Mol Ther 2013; 21 Suppl 1: s257.
41. [41] Imren S, Payen E, Westerman KA, et al. Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells. Proc Natl Acad Sci U S A 2002; 99: 14380-5.
42. [42] Deichmann A, Hacein-Bey-Abina S, Schmidt M, et al. Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. J Clin Invest 2007; 117: 2225-32.
43. [43] Biffi A, Bartolomae CC, Cesana D, et al. Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood 2011; 117: 5332-9.
44. [44] Tubsuwan A, Abed S, Deichmann A, et al. Parallel assessment of globin lentiviral transfer in induced pluripotent stem cells and adult hematopoietic stem cells derived from the same transplanted betathalassemia patient. Stem Cells 2013; 31: 1785-94.
45. [45] Kustikova O, Fehse B, Modlich U, et al. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 2005; 308: 1171-4.
46. [46] Schroder AR, Shinn P, Chen H, et al. HIV-1 integration in the human genome favors active genes and local hotspots. Cell 2002; 110: 521-9.
47. [47] Ciuffi A, Llano M, Poeschla E, et al. A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med 2005; 11: 1287-9.
48. [48] Marshall HM, Ronen K, Berry C, et al. Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting. PloS One 2007; 2: e1340.
49. [49] Ott MG, Schmidt M, Schwarzwaelder K, et al. Correction of Xlinked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med 2006; 12: 401-9.
50. [50] Avedillo Diez I, Zychlinski D, Coci EG, 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: 1525-37.
51. [51] Boztug K, Schmidt M, Schwarzer A, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. New Eng J Med 2010; 363: 1918-27.
52. [52] Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2- associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302: 415-9.
53. [53] Gold LS, Manley NB, Slone TH, et al. Compendium of chemical carcinogens by target organ: results of chronic bioassays in rats, mice, hamsters, dogs, and monkeys. Toxicol Pathol 2001; 29: 639-52.
54. [54] Taddesse-Heath L, Chattopadhyay SK, Dillehay DL, et al. Lymphomas and high-level expression of murine leukemia viruses in CFW mice. J Virol 2000; 74: 6832-7.
55. [55] Ward JM. Lymphomas and leukemias in mice. Exp Toxicol Pathol 2006; 57: 377-81.
56. [56] Will E, Bailey J, Schuesler T, et al. Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials. Mol Ther 2007; 15: 782-91.
57. [57] Boorman GA, Rafferty CN, Ward JM, et al. Leukemia and lymphoma incidence in rodents exposed to low-frequency magnetic fields. Radiat Res 2000; 153: 627-36.
58. [58] Ginn SL, Liao SH, Dane AP, et al. Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and gammac overexpression. Mol Ther 2010; 18: 965-76.