Regulatory and Exhausted T Cell Responses to AAV Capsid

Human Gene Therapy

Volumn 28, Issue 4, 2017, Pages 338-349

  Gernoux, Gwladys ^a   Wilson, James M ^b   Mueller, Christian ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

AAV; CTL; immune response; regulatory T cell; T cell exhaustion; Treg

Indexed keywords

ADENO ASSOCIATED VIRUS; ARTICLE; CLINICAL PROTOCOL; GENE TRANSFER; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; NONHUMAN; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; VIRUS CAPSID; ADVERSE EFFECTS; CELLULAR IMMUNITY; DEPENDOPARVOVIRUS; GENE THERAPY; GENE VECTOR; GENETICS; IMMUNOLOGY; THERAPEUTIC USE;

CAPSID PROTEIN;

CAPSID PROTEINS; DEPENDOVIRUS; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HUMANS; IMMUNITY, CELLULAR; T-LYMPHOCYTES;

EID: 85018473316     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.2017.022     Document Type: Article

References (81)

1. Jooss K, Yang Y, Fisher KJ, et al. Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J Virol 1998;72:4212-4223.
2. Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med 2006;12:342-347.
3. Mingozzi F, Maus MV, Hui DJ, et al. CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat Med 2007;13:419-422.
4. Snyder RO, Miao C, Meuse L, et al. Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors. Nat Med 1999;5:64-70.
5. Mount JD, Herzog RW, Tillson DM, et al. Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liverdirected gene therapy. Blood 2002;99:2670-2676.
6. Nathwani AC, Tuddenham EGD, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 2011;365: 2357-2365.
7. Spark Therapeutics. Spark Therapeutics and Pfizer present updated preliminary data from hemophilia B phase 1/2 trial suggesting consistent and sustained levels of factor IX activity at annual ASH meeting. Press release: http://ir.sparktx.com/phoenix.zhtml?c=253900&p=irol-newsArticle&ID= 2227316 (last accessed December 2016).
8. UniQure. Second-dose cohort demonstrates dose response with all patients free of prophylactic FIX replacement therapy and only one spontaneous bleed reported. Press release: https://tools.eurolandir.com/tools/Pressreleases/GetPress Release/?ID=3302307&lang=en-GB&companycode= nl-qure&v= (last accessed December 2016).
9. Mueller C, Chulay JD, Trapnell BC, et al. Human Treg responses allow sustained recombinant adenoassociated virus-mediated transgene expression. J Clin Invest 2013;123:5310-5318.
10. Ferreira V, Twisk J, Kwikkers K, et al. Immune responses to intramuscular administration of alipogene tiparvovec (AAV1-LPL(S447X)) in a Phase II clinical trial of lipoprotein lipase deficiency gene therapy. Hum Gene Ther 2014;25: 180-188.
11. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of selftolerance causes various autoimmune diseases. J Immunol 1995;155:1151-1164.
12. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003;3:253-257.
13. Flores-Borja F, Jury EC, Mauri C, et al. Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis. Proc Natl Acad Sci U S A 2008;105:19396-19401.
14. Zheng Y, Manzotti CN, Burke F, et al. Acquisition of suppressive function by activated human CD4+ CD25-T cells is associated with the expression of CTLA-4 not FoxP3. J Immunol 2008;181:1683-1691.
15. Baecher-Allan C, Wolf E, Hafler DA. MHC class II expression identifies functionally distinct human regulatory T cells. J Immunol 2006;176:4622-4631.
16. Borsellino G, Kleinewietfeld M, Di Mitri D, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 2007;110:1225-1232.
17. Liu W, Putnam AL, Xu-Yu Z, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 2006;203:1701-1711.
18. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057-1061.
19. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330-336.
20. Khattri R, Cox T, Yasayko S-A, et al. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003;4:337-342.
21. Thornton AM, Kilaru G, Burr P, et al. Helios expression defines two distinct populations of Foxp3+ regulatory T cells. J Immunol 2016;196:125.6.
22. Sebastian M, Lopez-Ocasio M, Metidji A, et al. Helios controls a limited subset of regulatory T cell functions. J Immunol 2016;196:144-155.
23. Piccirillo CA, Shevach EM. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol 2001;167:1137-1140.
24. Grossman WJ, Verbsky JW, Barchet W, et al. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004;21:589-601.
25. Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cellmediated suppression of tumor clearance. Immunity 2007;27:635-646.
26. Loebbermann J, Thornton H, Durant L, et al. Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection. Mucosal Immunol 2012;5: 161-172.
27. Cederbom L, Hall H, Ivars F. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur J Immunol 2000; 30:1538-1543.
28. Misra N, Bayry J, Lacroix-Desmazes S, et al. Cutting edge: human CD4+CD25+ T cells restrain the maturation and antigen-presenting function of dendritic cells. J Immunol 2004;172:4676-4680.
29. Onishi Y, Fehervari Z, Yamaguchi T, et al. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A 2008;105:10113-10118.
30. Tadokoro CE, Shakhar G, Shen S, et al. Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J Exp Med 2006; 203:505-511.
31. Tang Q, Adams JY, Tooley AJ, et al. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol 2006;7: 83-92.
32. Groux H, O'Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997;389:737-742.
33. Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25-naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198:1875-1886.
34. Collison LW, Chaturvedi V, Henderson AL, et al. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 2010;11:1093-1101.
35. Weiss L, Donkova-Petrini V, Caccavelli L, et al. Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 2004;104:3249-3256.
36. Xu D, Fu J, Jin L, et al. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol 2006;177:739-747.
37. van der Burg SH, Piersma SJ, de Jong A, et al. Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens. Proc Natl Acad Sci U S A 2007;104:12087-12092.
38. Cabrera R, Tu Z, Xu Y, et al. An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology 2004;40:1062-1071.
39. Lechner F, Wong DKH, Dunbar PR, et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 2000;191:1499-1512.
40. Zajac AJ, Blattman JN, Murali-Krishna K, et al. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 1998;188:2205-2213.
41. Wherry EJ. T cell exhaustion. Nat Immunol 2011;12:492-499.
42. Blackburn SD, Shin H, Haining WN, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 2009;10:29-37.
43. Velazquez VM, Bowen DG, Walker CM. Silencing of T lymphocytes by antigen-driven programmed death in recombinant adeno-associated virus vector-mediated gene therapy. Blood 2009;113: 538-545.
44. Lin J, Zhi Y, Mays L, et al. Vaccines based on novel adeno-associated virus vectors elicit aberrant CD8+ T-cell responses in mice. J Virol 2007; 81:11840-11849.
45. Lin S-W, Hensley SE, Tatsis N, et al. Recombinant adeno-associated virus vectors induce functionally impaired transgene product-specific CD8+ T cells in mice. J Clin Invest 2007;117:3958-3970.
46. Flotte TR, Trapnell BC, Humphries M, et al. Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing a1-antitrypsin: interim results. Hum Gene Ther 2011;22:1239-1247.
47. Mueller C, Gernoux G, Gruntman AM, et al. 5 Year expression and neutrophil defect repair after gene therapy in alpha-1 antitrypsin deficiency. Mol Ther 2017; [Epub ahead of print] DOI: 10.1016/j.ymthe.2017.03.029
48. Stroes ES, Nierman MC, Meulenberg JJ, et al. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol 2008;28:2303-2304.
49. Mingozzi F, Meulenberg JJ, Hui DJ, et al. AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. Blood 2009;114:2077-2086.
50. Wang Z, Kuhr CS, Allen JM, et al. Sustained AAVmediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression. Mol Ther 2007;15: 1160-1166.
51. Wang Z, Storb R, Halbert CL, et al. Successful regional delivery and long-term expression of a dystrophin gene in canine muscular dystrophy: a preclinical model for human therapies. Mol Ther 2012;20:1501-1507.
52. Mingozzi F, Hasbrouck NC, Basner-Tschakarjan E, et al. Modulation of tolerance to the transgene product in a nonhuman primate model of AAVmediated gene transfer to liver. Blood 2007;110: 2334-2341.
53. Nathwani AC, Reiss UM, Tuddenham EGD, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014;371: 1994-2004.
54. Flanigan KM, Campbell K, Viollet L, et al. Antidystrophin T cell responses in Duchenne muscular dystrophy: prevalence and a glucocorticoid treatment effect. Hum Gene Ther 2013;24:797-806.
55. Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, et al. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol 2009;66:290-297.
56. Mendell JR, Campbell K, Rodino-Klapac L, et al. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 2010;363:1429-1437.
57. Mendell JR, Al-Zaidy S, Shell R, et al. 480. Gene therapy for spinal muscular atrophy type 1 shows potential to improve survival and motor functional outcomes. Mol Ther 2016;24:S190.
58. Zhu J, Huang X, Yang Y. The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice. J Clin Invest 2009;119:2388-2398.
59. Aldrich WA, Ren C, White AF, et al. Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with selfcomplementary adeno-associated virus 6 combined with immunostimulatory ligands. Gene Ther 2006;13:29-39.
60. Veron P, Allo V, Riviere C, et al. Major subsets of human dendritic cells are efficiently transduced by self-complementary adeno-associated virus vectors 1 and 2. J Virol 2007;81:5385-5394.
61. Veron P, Boutin S, Martin S, et al. Highly efficient transduction of human plasmacytoid dendritic cells without phenotypic and functional maturation. J Transl Med 2009;7:10.
62. Gernoux G, Guilbaud M, Dubreil L, et al. Early interaction of adeno-associated virus serotype 8 vector with the host immune system following intramuscular delivery results in weak but detectable lymphocyte and dendritic cell transduction. Hum Gene Ther 2015;26:1-13.
63. Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther 2010;21:704-712.
64. Veron P, Leborgne C, Monteilhet V, et al. Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors. J Immunol 2012;188:6418-6424.
65. Mays LE, Wang L, Lin J, et al. AAV8 induces tolerance in murine muscle as a result of poor APC transduction, T cell exhaustion, and minimal MHCI upregulation on target cells. Mol Ther 2014;22:28-41.
66. Pandya J, Ortiz L, Ling C, et al. Rationally designed capsid and transgene cassette of AAV6 vectors for dendritic cell-based cancer immunotherapy. Immunol Cell Biol 2014;92:116-123.
67. Pandya M, Britt K, Hoffman B, et al. Reprogramming immune response with capsid-optimized AAV6 vectors for immunotherapy of cancer. J Immunother 2015;38:292-298.
68. Li H, Tuyishime S, Wu T-L, et al. Adeno-associated virus vectors serotype 2 induce prolonged proliferation of capsid-specific CD8+ T cells in mice. Mol Ther 2011;19:536-546.
69. Stieger K, Schroeder J, Provost N, et al. Detection of intact rAAV particles up to 6 years after successful gene transfer in the retina of dogs and primates. Mol Ther 2009;17:516-523.
70. Ozeri E, Mizrahi M, Shahaf G, et al. a-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol 2012;189:146-153.
71. Whartenby KA, Calabresi PA, McCadden E, et al. Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc Natl Acad Sci U S A 2005;102:16741-16746.
72. Rodionova E, Conzelmann M, Maraskovsky E, et al. GSK-3 mediates differentiation and activation of proinflammatory dendritic cells. Blood 2007;109:1584-1592.
73. Oderup C, LaJevic M, Butcher EC. Canonical and noncanonical Wnt proteins program dendritic cell responses for tolerance. J Immunol 2013;190: 6126-6134.
74. Battaglia M, Stabilini A, Migliavacca B, et al. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006;177:8338-8347.
75. Biomarin. BioMarin provides encouraging preliminary data on first 8 patients in hemophilia A gene therapy program. Press release: https://globenewswire.com/news-release/2016/04/20/830721/0/en/BioMarin-Provides-Encouraging-Preliminary-Data-on-First-8-Patients-in-Hemophilia-A-Gene-Therapy-Program.html (last accessed December 2016).
76. Gaudet D, Méthot J, Déry S, et al. Efficacy and longtermsafety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther 2013;20:361-369.
77. McPhee SWJ, Janson CG, Li C, et al. Immune responses to AAV in a Phase I study for Canavan disease. J Gene Med 2006;8:577-588.
78. Tardieu M, Zérah M, Husson B, et al. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a Phase I/II trial. Hum Gene Ther 2014;25:506-516.
79. Simonelli F, Maguire AM, Testa F, et al. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther 2010;18:643-650.
80. Brantly ML, Spencer LT, Humphries M, et al. Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Hum Gene Ther 2006;17:1177-1186.
81. Manno CS, Chew AJ, Hutchison S, et al. AAVmediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 2003;101:2963-2972.