Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.
adeno-associated virus
bioanalytical methodologies and validation strategies
clinical mitigation
gene therapy
immunogenicity
nonclinical and clinical outcomes
risk assessment
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
08 Sep 2022
08 Sep 2022
Historique:
entrez:
12
9
2022
pubmed:
13
9
2022
medline:
13
9
2022
Statut:
epublish
Résumé
Immunogenicity has imposed a challenge to efficacy and safety evaluation of adeno-associated virus (AAV) vector-based gene therapies. Mild to severe adverse events observed in clinical development have been implicated with host immune responses against AAV gene therapies, resulting in comprehensive evaluation of immunogenicity during nonclinical and clinical studies mandated by health authorities. Immunogenicity of AAV gene therapies is complex due to the number of risk factors associated with product components and pre-existing immunity in human subjects. Different clinical mitigation strategies have been employed to alleviate treatment-induced or -boosted immunogenicity in order to achieve desired efficacy, reduce toxicity, or treat more patients who are seropositive to AAV vectors. In this review, the immunogenicity risk assessment, manifestation of immunogenicity and its impact in nonclinical and clinical studies, and various clinical mitigation strategies are summarized. Last, we present bioanalytical strategies, methodologies, and assay validation applied to appropriately monitor immunogenicity in AAV gene therapy-treated subjects.
Identifiants
pubmed: 36092368
doi: 10.1016/j.omtm.2022.07.018
pii: S2329-0501(22)00110-3
pmc: PMC9418752
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
471-494Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Mol Ther. 2005 Jun;11(6):875-88
pubmed: 15922958
J Hepatol. 2021 Mar;74(3):560-566
pubmed: 33186633
Nat Med. 2007 Apr;13(4):419-22
pubmed: 17369837
Mol Ther. 2018 Jan 3;26(1):173-183
pubmed: 28943274
Mol Ther Methods Clin Dev. 2020 May 13;17:1139-1154
pubmed: 32490035
Pharmacol Ther. 2020 Mar;207:107453
pubmed: 31836454
Mol Ther. 2004 Feb;9(2):231-40
pubmed: 14759807
Sci Transl Med. 2020 Nov 11;12(569):
pubmed: 33177182
Mol Ther. 2005 Jun;11(6):889-98
pubmed: 15922959
Front Immunol. 2021 Apr 13;12:666666
pubmed: 33927727
Mol Ther Methods Clin Dev. 2017 Dec 01;8:87-104
pubmed: 29326962
Hepatology. 2012 Jan;55(1):287-97
pubmed: 21898480
Nat Med. 1999 Jan;5(1):56-63
pubmed: 9883840
J Virol. 2002 May;76(9):4580-90
pubmed: 11932423
J Infect Dis. 2009 Feb 1;199(3):381-90
pubmed: 19133809
J Toxicol Sci. 2021;46(2):57-68
pubmed: 33536390
J Clin Invest. 2013 Mar;123(3):1390-401
pubmed: 23454772
Front Immunol. 2021 May 17;12:675897
pubmed: 34084173
J Clin Invest. 2018 Dec 3;128(12):5267-5279
pubmed: 30352429
J Vis Exp. 2018 Sep 10;(139):
pubmed: 30247460
Expert Opin Biol Ther. 2022 Apr 3;:1-5
pubmed: 35373689
Gene Ther. 2013 May;20(5):497-503
pubmed: 22855092
Mol Ther. 2014 Feb;22(2):338-347
pubmed: 24196577
N Engl J Med. 2021 Apr 8;384(14):1323-1334
pubmed: 33826820
Mol Ther Methods Clin Dev. 2019 Dec 25;17:198-208
pubmed: 31970198
Hum Gene Ther. 2010 Jun;21(6):704-12
pubmed: 20095819
AAPS J. 2016 Nov;18(6):1335-1350
pubmed: 27495119
Front Immunol. 2021 Apr 01;12:658038
pubmed: 33868303
J Clin Invest. 2021 Jan 4;131(1):
pubmed: 33393506
Nat Rev Drug Discov. 2019 May;18(5):358-378
pubmed: 30710128
Hum Gene Ther. 2016 Nov;27(11):916-925
pubmed: 27412455
Mol Ther Methods Clin Dev. 2018 Nov 29;13:40-46
pubmed: 30623003
Hum Gene Ther. 2017 Nov;28(11):1061-1074
pubmed: 28835127
Hum Gene Ther Methods. 2013 Apr;24(2):59-67
pubmed: 23442094
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7827-32
pubmed: 18511559
J Virol. 2013 Oct;87(19):10784-91
pubmed: 23903832
Mol Ther Methods Clin Dev. 2022 Jan 07;24:222-229
pubmed: 35141351
Front Immunol. 2014 Mar 03;5:82
pubmed: 24624131
Hum Gene Ther. 2018 Nov;29(11):1235-1241
pubmed: 30132368
Mol Ther Methods Clin Dev. 2018 Oct 04;11:65-72
pubmed: 30397628
J Clin Invest. 2013 Dec;123(12):5310-8
pubmed: 24231351
PLoS One. 2009 Aug 04;4(8):e6376
pubmed: 19652717
Mol Immunol. 2019 Oct;114:341-352
pubmed: 31446305
J Pediatr. 2021 Apr;231:265-268
pubmed: 33259859
Viruses. 2019 Jan 25;11(2):
pubmed: 30691064
Curr Gene Ther. 2015;15(4):381-94
pubmed: 26122097
N Engl J Med. 2020 Jul 9;383(2):151-158
pubmed: 32640133
Mol Ther. 2007 Apr;15(4):792-800
pubmed: 17245353
Mol Ther. 2014 Nov;22(11):1900-9
pubmed: 25048217
Ther Adv Hematol. 2018 Aug 27;9(9):273-293
pubmed: 30210756
Hum Gene Ther. 2002 Jul 20;13(11):1281-91
pubmed: 12162811
Mol Ther. 2020 Aug 5;28(8):1756-1758
pubmed: 32710825
AAPS J. 2020 Jan 6;22(2):24
pubmed: 31907680
Mol Ther. 2021 Oct 6;29(10):2898-2909
pubmed: 34461297
J Virol. 2012 Jun;86(12):6620-31
pubmed: 22496229
Cold Spring Harb Perspect Biol. 2014 Sep 04;6(10):a016295
pubmed: 25190079
Blood. 2008 Jan 1;111(1):453-62
pubmed: 17967941
Blood. 2019 Feb 7;133(6):530-539
pubmed: 30510080
Blood Adv. 2017 Oct 16;1(23):2019-2031
pubmed: 29296848
Nat Rev Immunol. 2014 Jan;14(1):24-35
pubmed: 24336101
N Engl J Med. 2010 Oct 7;363(15):1429-37
pubmed: 20925545
Med Hypotheses. 2013 May;80(5):613-6
pubmed: 23484673
Front Immunol. 2014 Feb 07;5:28
pubmed: 24570676
Biotechnol J. 2021 Jan;16(1):e2000022
pubmed: 33146911
N Engl J Med. 2017 Nov 2;377(18):1713-1722
pubmed: 29091557
Blood. 2009 Sep 3;114(10):2077-86
pubmed: 19506302
Mol Ther. 2014 Jan;22(1):1-2
pubmed: 24384906
Mol Ther Methods Clin Dev. 2019 Jun 04;14:77-89
pubmed: 31309129
J Med Virol. 1999 Nov;59(3):406-11
pubmed: 10502275
Nat Biotechnol. 2020 Aug;38(8):910
pubmed: 32760031
Nat Rev Rheumatol. 2020 Mar;16(3):155-166
pubmed: 32034323
J Virol. 2008 Mar;82(6):2727-40
pubmed: 18199646
Mol Ther. 2011 May;19(5):876-85
pubmed: 21245849
Front Immunol. 2021 Mar 17;12:658399
pubmed: 33815421
Lupus. 2005;14 Suppl 1:s2-8
pubmed: 15803924
J Virol. 2006 Jan;80(2):821-34
pubmed: 16378984
Mol Ther. 2020 Mar 4;28(3):747-757
pubmed: 31982038
Mol Ther. 2021 Feb 3;29(2):597-610
pubmed: 33309883
Hum Gene Ther Methods. 2015 Apr;26(2):45-53
pubmed: 25819687
Methods Mol Biol. 2014;1172:235-42
pubmed: 24908310
Expert Rev Vaccines. 2011 Mar;10(3):299-306
pubmed: 21434798
Nat Rev Genet. 2014 Jul;15(7):445-51
pubmed: 24840552
Mol Ther. 2005 Nov;12(5):876-84
pubmed: 16005263
Mol Ther Methods Clin Dev. 2017 Jan 25;4:159-168
pubmed: 28345001
Nat Med. 2018 Jun;24(6):699
pubmed: 29867233
Mol Ther. 2020 Mar 4;28(3):723-746
pubmed: 31972133
Biomedicines. 2014 Mar 03;2(1):80-97
pubmed: 28548061
Mol Ther. 2006 Mar;13(3):517-27
pubmed: 16325474
Hum Gene Ther. 2020 Aug;31(15-16):787
pubmed: 32777938
Mol Ther. 2020 Mar 4;28(3):758-770
pubmed: 31780366
Ann Surg. 2018 Sep;268(3):488-496
pubmed: 30004918
J Thromb Haemost. 2020 May;18(5):1075-1080
pubmed: 32011092
J Clin Invest. 2009 Jun;119(6):1688-95
pubmed: 19436115
Gene Ther. 2012 Mar;19(3):288-94
pubmed: 21697954
Cell. 2021 Sep 16;184(19):4919-4938.e22
pubmed: 34506722
Sci Transl Med. 2021 Feb 10;13(580):
pubmed: 33568518
Hum Gene Ther. 2018 Mar;29(3):285-298
pubmed: 29378426
Hum Gene Ther. 2020 Aug;31(15-16):808-818
pubmed: 32845779
Immunity. 2009 Jun 19;30(6):832-44
pubmed: 19538929
Mol Ther Methods Clin Dev. 2015 Sep 30;2:15029
pubmed: 26445723
Annu Rev Virol. 2017 Sep 29;4(1):511-534
pubmed: 28961410
Mol Ther Methods Clin Dev. 2022 Jan 18;24:255-267
pubmed: 35211638
Cells. 2012 May 10;1(2):111-26
pubmed: 24710418
Mol Ther. 2010 Jan;18(1):135-42
pubmed: 19904235
Hum Gene Ther. 2011 May;22(5):605-12
pubmed: 21222531
Blood. 2018 Mar 1;131(9):1022-1031
pubmed: 29246900
Invest Ophthalmol Vis Sci. 2018 Apr 1;59(5):1910-1915
pubmed: 29677353
J Innate Immun. 2015;7(3):302-14
pubmed: 25612611
Mol Ther Methods Clin Dev. 2021 May 29;22:183-195
pubmed: 34485604
Cell Immunol. 2019 Aug;342:103722
pubmed: 29195742
AAPS J. 2021 Sep 16;23(6):108
pubmed: 34529177
Expert Rev Vaccines. 2011 Apr;10(4):499-511
pubmed: 21506647
Pharmaceutics. 2021 Apr 20;13(4):
pubmed: 33923984
Genome Biol. 2002 Jul 29;3(8):REVIEWS3011
pubmed: 12186654
Cell Immunol. 2019 Aug;342:103682
pubmed: 28888664
Cell Immunol. 2019 Aug;342:103658
pubmed: 28645365
J Immunotoxicol. 2009 Dec;6(4):227-34
pubmed: 19908941
Nat Med. 2021 Nov;27(11):1982-1989
pubmed: 34663988
Gene Ther. 2005 Oct;12(19):1453-64
pubmed: 15889137
Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):41
pubmed: 33630023
J Immunol Res. 2016;2016:6262383
pubmed: 27556048
Hum Gene Ther. 2011 Nov;22(11):1389-401
pubmed: 21476868
Int J Mol Sci. 2021 Aug 25;22(17):
pubmed: 34502108
Mol Ther. 2020 Mar 4;28(3):709-722
pubmed: 31968213
Front Immunol. 2020 Jan 21;10:3110
pubmed: 32038634
Mol Ther Methods Clin Dev. 2021 Jun 12;22:162-171
pubmed: 34485602
JCI Insight. 2018 Jun 21;3(12):
pubmed: 29925692
Pharmacol Rep. 2020 Oct;72(5):1227-1263
pubmed: 32691346
Nat Med. 2020 Jul;26(7):1096-1101
pubmed: 32483358
Blood. 2004 Aug 15;104(4):969-77
pubmed: 15105293
J Virol. 2013 Dec;87(23):13035-41
pubmed: 24027330
Blood. 2011 Jun 16;117(24):6459-68
pubmed: 21474674
J Virol. 2017 Jan 31;91(4):
pubmed: 27928011
Mol Ther Nucleic Acids. 2022 Mar 21;28:293-306
pubmed: 35474733
Mol Ther Methods Clin Dev. 2019 Jun 07;14:126-133
pubmed: 31338384
Blood. 2021 Feb 11;137(6):763-774
pubmed: 33067633
Mol Ther Methods Clin Dev. 2019 Apr 11;13:440-452
pubmed: 31193016
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):E5076-85
pubmed: 25385646
Vaccine. 2014 Nov 12;32(48):6377-89
pubmed: 24975812
Hum Gene Ther. 2017 Apr;28(4):328-337
pubmed: 28042943
Hum Gene Ther. 2019 Aug;30(8):957-966
pubmed: 31017018
Blood. 2013 Mar 21;121(12):2224-33
pubmed: 23325831
N Engl J Med. 2011 Dec 22;365(25):2357-65
pubmed: 22149959
Lancet. 2017 Aug 26;390(10097):849-860
pubmed: 28712537
Mol Ther. 2020 Mar 4;28(3):701-703
pubmed: 32035026
Mol Ther. 2011 Nov;19(11):2021-30
pubmed: 21587208
J Oncol. 2010;2010:426218
pubmed: 20049168
Mol Ther. 2011 Nov;19(11):2084-91
pubmed: 21629225
Gene Ther. 2013 Apr;20(4):361-9
pubmed: 22717743
N Engl J Med. 2014 Nov 20;371(21):1994-2004
pubmed: 25409372
Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1655-1659
pubmed: 28137880
Immunology. 2007 Jan;120(1):120-32
pubmed: 17083604
Bioanalysis. 2018 Jun 1;10(11):803-814
pubmed: 29637799
Mol Ther Methods Clin Dev. 2019 Jan 26;12:248-265
pubmed: 30815511
Curr Gene Ther. 2014;14(2):86-100
pubmed: 24588706
AAPS J. 2016 Mar;18(2):311-20
pubmed: 26821802
J Clin Invest. 2013 Jul;123(7):2994-3001
pubmed: 23778142
Mol Ther. 2017 Dec 6;25(12):2648-2660
pubmed: 28970046
Methods Mol Biol. 2012;820:7-23
pubmed: 22131023
Transplantation. 2012 Jul 27;94(2):123-31
pubmed: 22743548
Mol Ther. 2012 Mar;20(3):572-9
pubmed: 22186792
Front Immunol. 2020 Apr 17;11:670
pubmed: 32362898
Hum Gene Ther Methods. 2015 Jun;26(3):103-5
pubmed: 26067568
N Engl J Med. 2017 Dec 7;377(23):2215-2227
pubmed: 29211678
Blood. 2007 Aug 15;110(4):1132-40
pubmed: 17438084
JCI Insight. 2020 Sep 17;5(19):
pubmed: 32941184
Hum Gene Ther. 2011 Oct;22(10):1239-47
pubmed: 21609134
J Immunol Methods. 2007 Apr 10;321(1-2):1-18
pubmed: 17307199
J Clin Invest. 2009 Aug;119(8):2388-98
pubmed: 19587448
Am J Transplant. 2012 Dec;12(12):3449-61
pubmed: 22994804
Blood. 2006 Nov 15;108(10):3321-8
pubmed: 16868252
Gene Ther. 2022 Feb;29(1-2):41-54
pubmed: 33432123
Cell Immunol. 2019 Dec;346:103997
pubmed: 31703913
J Clin Invest. 2003 May;111(9):1347-56
pubmed: 12727926
Drugs. 2019 Feb;79(3):347-352
pubmed: 30767127
Toxicol Pathol. 2018 Dec;46(8):1020-1027
pubmed: 30295175
Genet Med. 2015 Nov;17(11):912-8
pubmed: 25741864
Annu Rev Immunol. 2014;32:433-59
pubmed: 24499275
AAPS J. 2008 Sep;10(3):439-49
pubmed: 18709516
Gene Ther. 2017 Dec;24(12):768-778
pubmed: 29106404
N Engl J Med. 2013 Jun 6;368(23):2169-81
pubmed: 23738544
Mol Ther Methods Clin Dev. 2018 Feb 13;9:119-129
pubmed: 29766022
Clin Diagn Lab Immunol. 2003 Nov;10(6):982-9
pubmed: 14607856
Nat Med. 2006 Mar;12(3):342-7
pubmed: 16474400
J Immunol Methods. 2011 Oct 28;373(1-2):45-53
pubmed: 21846471
Hum Mol Genet. 2019 Oct 1;28(R1):R3-R14
pubmed: 31261383
Clin Vaccine Immunol. 2011 Sep;18(9):1586-8
pubmed: 21775517
Mol Ther. 2010 Nov;18(11):1907-16
pubmed: 20700109
J Gene Med. 2006 Feb;8(2):155-62
pubmed: 16285001
Mol Ther. 2017 Apr 5;25(4):880-891
pubmed: 28284982
Mol Ther Methods Clin Dev. 2020 Jan 21;16:179-191
pubmed: 32055646
Hum Gene Ther Clin Dev. 2017 Dec;28(4):208-218
pubmed: 29160099
J Immunol Methods. 2003 Dec;283(1-2):91-8
pubmed: 14659902