Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

Molecular Therapy Methods and Clinical Development

Volumn 3, Issue , 2016, Pages 15056-

  Lytle, Allison M ^a   Brown, Harrison C ^a   Paik, Na Yoon ^b   Knight, Kristopher A ^b   Wright, J Fraser ^c,d   Spencer, H Trent ^b   Doering, Christopher B ^b  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENO ASSOCIATED VIRUS VECTOR; APOLIPOPROTEIN E; BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 8 ANTIBODY; BLOOD CLOTTING FACTOR 9;

ADAPTIVE IMMUNITY; ANIMAL MODEL; ANTIBODY TITER; ARTICLE; CONTROLLED STUDY; GENE DOSAGE; GENE TRANSFER; HEMATOPOIETIC STEM CELL; HEMOPHILIA A; HEMOPHILIA B; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOMODULATION; LIVER CELL; MEMORY CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; VIRAL GENE THERAPY;

EID: 84978812122     PISSN: None     EISSN: 23290501     Source Type: Journal    
DOI: 10.1038/mtm.2015.56     Document Type: Article

References (61)

1. 1 Lollar, P, Pathogenic antibodies to coagulation factors. Part one: factor VIII and factor IX. J Thromb Haemost 2 (2004), 1082–1095.
2. 2 Meeks, SL, Chapman, RL, Kempton, C, Dunn, AL, Late immune tolerance induction in haemophilia A patients. Haemophilia 19 (2013), 445–448.
3. 3 Hausl, C, Ahmad, RU, Sasgary, M, Doering, CB, Lollar, P, Richter, G, et al. High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors. Blood 106 (2005), 3415–3422.
4. 4 Sakurai, Y, Shima, M, Tanaka, I, Fukuda, K, Yoshida, K, Yoshioka, A, Association of anti-idiotypic antibodies with immune tolerance induction for the treatment of hemophilia A with inhibitors. Haematologica 89 (2004), 696–703.
5. 5 Mueller, SN, Ahmed, R, High antigen levels are the cause of T cell exhaustion during chronic viral infection. Proc Natl Acad Sci USA 106 (2009), 8623–8628.
6. 6 Waters, B, Lillicrap, D, The molecular mechanisms of immunomodulation and tolerance induction to factor VIII. J Thromb Haemost 7 (2009), 1446–1456.
7. 7 Tomita, Y, Khan, A, Sykes, M, Role of intrathymic clonal deletion and peripheral anergy in transplantation tolerance induced by bone marrow transplantation in mice conditioned with a nonmyeloablative regimen. J Immunol 153 (1994), 1087–1098.
8. 8 Racine, J, Wang, M, Zhang, C, Lin, CL, Liu, H, Todorov, I, et al. Induction of mixed chimerism with MHC-mismatched but not matched bone marrow transplants results in thymic deletion of host-type autoreactive T-cells in NOD mice. Diabetes 60 (2011), 555–564.
9. + T cells in tolerance to the transgene product following hepatic in vivo gene transfer. Blood 110 (2007), 1132–1140.
10. 10 Markusic, DM, Hoffman, BE, Perrin, GQ, Nayak, S, Wang, X, LoDuca, PA, et al. Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies. EMBO Mol Med 5 (2013), 1698–1709.
11. 11 Annoni, A, Cantore, A, Della Valle, P, Goudy, K, Akbarpour, M, Russo, F, et al. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice. EMBO Mol Med 5 (2013), 1684–1697.
12. 12 Aiuti, A, Biasco, L, Scaramuzza, S, Ferrua, F, Cicalese, MP, Baricordi, C, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science, 341, 2013, 1233151.
13. 13 Biffi, A, Montini, E, Lorioli, L, Cesani, M, Fumagalli, F, Plati, T, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science, 341, 2013, 1233158.
14. 14 Monahan, PE, Sun, J, Gui, T, Hu, G, Hannah, WB, Wichlan, DG, et al. Employing a gain-of-function factor IX variant R338L to advance the efficacy and safety of hemophilia B human gene therapy: preclinical evaluation supporting an ongoing adeno-associated virus clinical trial. Hum Gene Ther 26 (2015), 69–81.
15. 15 Nathwani, AC, Tuddenham, EG, Rangarajan, S, Rosales, C, McIntosh, J, Linch, DC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 365 (2011), 2357–2365.
16. 16 Brantly, ML, Chulay, JD, Wang, L, Mueller, C, Humphries, M, Spencer, LT, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci USA 106 (2009), 16363–16368.
17. 17 Nathwani, AC, Rosales, C, McIntosh, J, Rastegarlari, G, Nathwani, D, Raj, D, et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther 19 (2011), 876–885.
18. 18 Embury, JE, Charron, CE, Martynyuk, A, Zori, AG, Liu, B, Ali, SF, et al. PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pah(enu2) mice. Brain Res 1127 (2007), 136–150.
19. 19 Rockwell, HE, McCurdy, VJ, Eaton, SC, Wilson, DU, Johnson, AK, Randle, AN, et al. AAV-mediated gene delivery in a feline model of Sandhoff disease corrects lysosomal storage in the central nervous system. ASN Neuro, 7, 2015, 2.
20. 20 Bennett, J, Ashtari, M, Wellman, J, Marshall, KA, Cyckowski, LL, Chung, DC, et al. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med, 4, 2012, 120ra15.
21. 21 High, KH, Nathwani, A, Spencer, T, Lillicrap, D, Current status of haemophilia gene therapy. Haemophilia 20:suppl. 4 (2014), 43–49.
22. 22 Brown, HC, Wright, JF, Zhou, S, Lytle, AM, Shields, JE, Spencer, HT, et al. Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery. Mol Ther Methods Clin Dev, 1, 2014, 14036.
23. 23 Doering, CB, Denning, G, Dooriss, K, Gangadharan, B, Johnston, JM, Kerstann, KW, et al. Directed engineering of a high-expression chimeric transgene as a strategy for gene therapy of hemophilia A. Mol Ther 17 (2009), 1145–1154.
24. 24 Doering, CB, Gangadharan, B, Dukart, HZ, Spencer, HT, Hematopoietic stem cells encoding porcine factor VIII induce pro-coagulant activity in hemophilia A mice with pre-existing factor VIII immunity. Mol Ther 15 (2007), 1093–1099.
25. 25 Ide, LM, Gangadharan, B, Chiang, KY, Doering, CB, Spencer, HT, Hematopoietic stem-cell gene therapy of hemophilia A incorporating a porcine factor VIII transgene and nonmyeloablative conditioning regimens. Blood 110 (2007), 2855–2863.
26. 26 Ide, LM, Iwakoshi, NN, Gangadharan, B, Jobe, S, Moot, R, McCarty, D, et al. Functional aspects of factor VIII expression after transplantation of genetically-modified hematopoietic stem cells for hemophilia A. J Gene Med 12 (2010), 333–344.
27. 27 Gangadharan, B, Parker, ET, Ide, LM, Spencer, HT, Doering, CB, High-level expression of porcine factor VIII from genetically modified bone marrow-derived stem cells. Blood 107 (2006), 3859–3864.
28. 28 Doering, CB, Healey, JF, Parker, ET, Barrow, RT, Lollar, P, High level expression of recombinant porcine coagulation factor VIII. J Biol Chem 277 (2002), 38345–38349.
29. 29 Doering, CB, Healey, JF, Parker, ET, Barrow, RT, Lollar, P, Identification of porcine coagulation factor VIII domains responsible for high level expression via enhanced secretion. J Biol Chem 279 (2004), 6546–6552.
30. 30 McIntosh, J, Lenting, PJ, Rosales, C, Lee, D, Rabbanian, S, Raj, D, et al. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant. Blood 121 (2013), 3335–3344.
31. 31 Sabatino, DE, Lange, AM, Altynova, ES, Sarkar, R, Zhou, S, Merricks, EP, et al. Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors. Mol Ther 19 (2011), 442–449.
32. 32 Ishiwata, A, Mimuro, J, Mizukami, H, Kashiwakura, Y, Takano, K, Ohmori, T, et al. Liver-restricted expression of the canine factor VIII gene facilitates prevention of inhibitor formation in factor VIII-deficient mice. J Gene Med 11 (2009), 1020–1029.
33. 33 Nathwani, AC, Reiss, UM, Tuddenham, EG, Rosales, C, Chowdary, P, McIntosh, J, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 371 (2014), 1994–2004.
34. 34 Manno, CS, Pierce, GF, Arruda, VR, Glader, B, Ragni, M, Rasko, JJ, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 12 (2006), 342–347.
35. 35 Slifka, MK, Antia, R, Whitmire, JK, Ahmed, R, Humoral immunity due to long-lived plasma cells. Immunity 8 (1998), 363–372.
36. 36 Finn, JD, Ozelo, MC, Sabatino, DE, Franck, HW, Merricks, EP, Crudele, JM, et al. Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy. Blood 116 (2010), 5842–5848.
37. 37 Rogers, GL, Herzog, RW, Gene therapy for hemophilia. Front Biosci (Landmark Ed) 20 (2015), 556–603.
38. 38 Ohmori, T, Mizukami, H, Ozawa, K, Sakata, Y, Nishimura, S, New approaches to gene and cell therapy for hemophilia. J Thromb Haemost 13:suppl. 1 (2015), S133–S142.
39. 39 Doering, CB, Spencer, HT, Replacing bad (F)actors: hemophilia. Hematology Am Soc Hematol Educ Program 2014 (2014), 461–467.
40. 40 Roncarolo, MG, Gregori, S, Lucarelli, B, Ciceri, F, Bacchetta, R, Clinical tolerance in allogeneic hematopoietic stem cell transplantation. Immunol Rev 241 (2011), 145–163.
41. 41 Ruiz, P, Maldonado, P, Hidalgo, Y, Gleisner, A, Sauma, D, Silva, C, et al. Transplant tolerance: new insights and strategies for long-term allograft acceptance. Clin Dev Immunol, 2013, 2013, 210506.
42. th annual Samuel Jason Mixter Lecture. Arch Surg 146 (2011), 501–505.
43. 43 Moayeri, M, Hawley, TS, Hawley, RG, Correction of murine hemophilia a by hematopoietic stem cell gene therapy. Mol Ther 12 (2005), 1034–1042.
44. 44 Moayeri, M, Ramezani, A, Morgan, RA, Hawley, TS, Hawley, RG, Sustained phenotypic correction of hemophilia a mice following oncoretroviral-mediated expression of a bioengineered human factor VIII gene in long-term hematopoietic repopulating cells. Mol Ther 10 (2004), 892–902.
45. 45 Mingozzi, F, Liu, YL, Dobrzynski, E, Kaufhold, A, Liu, JH, Wang, Y, et al. Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer. J Clin Invest 111 (2003), 1347–1356.
46. 46 Iqbal, AJ, McNeill, E, Kapellos, TS, Regan-Komito, D, Norman, S, Burd, S, et al. Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo. Blood 124 (2014), e33–e44.
47. 47 Niemeyer, GP, Herzog, RW, Mount, J, Arruda, VR, Tillson, DM, Hathcock, J, et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood 113 (2009), 797–806.
48. 48 Crudele, JM, Finn, JD, Siner, JI, Martin, NB, Niemeyer, GP, Zhou, S, et al. AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood 125 (2015), 1553–1561.
49. 49 Brown, HC, Gangadharan, B, Doering, CB, Enhanced biosynthesis of coagulation factor VIII through diminished engagement of the unfolded protein response. J Biol Chem 286 (2011), 24451–24457.
50. 50 Sack, BK, Merchant, S, Markusic, DM, Nathwani, AC, Davidoff, AM, Byrne, BJ, et al. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy. PLoS One, 7, 2012, e37671.
51. + regulatory T cells induced by an agonist self-peptide. Nat Immunol 2 (2001), 301–306.
52. 52 Shkap, V, Molad, T, Brayton, KA, Brown, WC, Palmer, GH, Expression of major surface protein 2 variants with conserved T-cell epitopes in Anaplasma centrale vaccinates. Infect Immun 70 (2002), 642–648.
53. 53 Bi, L, Lawler, AM, Antonarakis, SE, High, KA, Gearhart, JD, Kazazian, HH Jr., Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nat Genet 10 (1995), 119–121.
54. 54 Nakanishi, T, Kuroiwa, A, Yamada, S, Isotani, A, Yamashita, A, Tairaka, A, et al. FISH analysis of 142 EGFP transgene integration sites into the mouse genome. Genomics 80 (2002), 564–574.
55. 55 Johnston, JM, Denning, G, Moot, R, Whitehead, D, Shields, J, Le Doux, JM, et al. High-throughput screening identifies compounds that enhance lentiviral transduction. Gene Ther 21 (2014), 1008–1020.
56. 56 Ayuso, E, Mingozzi, F, Montane, J, Leon, X, Anguela, XM, Haurigot, V, et al. High AAV vector purity results in serotype- and tissue-independent enhancement of transduction efficiency. Gene Ther 17 (2010), 503–510.
57. 57 Matsushita, T, Elliger, S, Elliger, C, Podsakoff, G, Villarreal, L, Kurtzman, GJ, et al. Adeno-associated virus vectors can be efficiently produced without helper virus. Gene Ther 5 (1998), 938–945.
58. 58 Wright, JF, Le, T, Prado, J, Bahr-Davidson, J, Smith, PH, Zhen, Z, et al. Identification of factors that contribute to recombinant AAV2 particle aggregation and methods to prevent its occurrence during vector purification and formulation. Mol Ther 12 (2005), 171–178.
59. 59 Parker, ET, Healey, JF, Barrow, RT, Craddock, HN, Lollar, P, Reduction of the inhibitory antibody response to human factor VIII in hemophilia A mice by mutagenesis of the A2 domain B-cell epitope. Blood 104 (2004), 704–710.
60. 60 Meeks, SL, Healey, JF, Parker, ET, Barrow, RT, Lollar, P, Non-classical anti-factor VIII C2 domain antibodies are pathogenic in a murine in vivo bleeding model. J Thromb Haemost 7 (2009), 658–664.
61. 61 Kasper, CK, Aledort, L, Aronson, D, Counts, R, Edson, JR, van Eys, J, et al. Proceedings: a more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh, 34, 1975, 612.