Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper

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...

Full description

Bibliographic Details
Main Authors: Tong-yuan Yang, Manuela Braun, Wibke Lembke, Fraser McBlane, John Kamerud, Stephen DeWall, Edit Tarcsa, Xiaodong Fang, Lena Hofer, Uma Kavita, Vijay V. Upreti, Swati Gupta, LiNa Loo, Alison J. Johnson, Rakesh Kantilal Chandode, Kay-Gunnar Stubenrauch, Maya Vinzing, Cindy Q. Xia, Vibha Jawa
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:Molecular Therapy: Methods & Clinical Development
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2329050122001103
_version_ 1818517229409402880
author Tong-yuan Yang
Manuela Braun
Wibke Lembke
Fraser McBlane
John Kamerud
Stephen DeWall
Edit Tarcsa
Xiaodong Fang
Lena Hofer
Uma Kavita
Vijay V. Upreti
Swati Gupta
LiNa Loo
Alison J. Johnson
Rakesh Kantilal Chandode
Kay-Gunnar Stubenrauch
Maya Vinzing
Cindy Q. Xia
Vibha Jawa
author_facet Tong-yuan Yang
Manuela Braun
Wibke Lembke
Fraser McBlane
John Kamerud
Stephen DeWall
Edit Tarcsa
Xiaodong Fang
Lena Hofer
Uma Kavita
Vijay V. Upreti
Swati Gupta
LiNa Loo
Alison J. Johnson
Rakesh Kantilal Chandode
Kay-Gunnar Stubenrauch
Maya Vinzing
Cindy Q. Xia
Vibha Jawa
author_sort Tong-yuan Yang
collection DOAJ
description 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.
first_indexed 2024-12-11T00:53:26Z
format Article
id doaj.art-1b85bb2274f44631a3d3b829f5704b0f
institution Directory Open Access Journal
issn 2329-0501
language English
last_indexed 2024-12-11T00:53:26Z
publishDate 2022-09-01
publisher Elsevier
record_format Article
series Molecular Therapy: Methods & Clinical Development
spelling doaj.art-1b85bb2274f44631a3d3b829f5704b0f2022-12-22T01:26:33ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012022-09-0126471494Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paperTong-yuan Yang0Manuela Braun1Wibke Lembke2Fraser McBlane3John Kamerud4Stephen DeWall5Edit Tarcsa6Xiaodong Fang7Lena Hofer8Uma Kavita9Vijay V. Upreti10Swati Gupta11LiNa Loo12Alison J. Johnson13Rakesh Kantilal Chandode14Kay-Gunnar Stubenrauch15Maya Vinzing16Cindy Q. Xia17Vibha Jawa18Janssen R&D LLC, Spring House, PA 19477, USA; Corresponding author Tong-yuan Yang, Preclinical Sciences and Translational Safety, Janssen R&D LLC., 1400 McKean Road, Spring House, PA 19477, USA.Bayer AG, Pharmaceuticals R&D, Berlin 13342, Germany; Corresponding author Manuela Braun, Bayer AG, Pharmaceuticals R&D, Muellerstr. 178, Berlin 13342, Germany.UCB Farchim SA, Bulle 1630, SwitzerlandNovartis, Basel 4056, SwitzerlandPfizer BioMedicine Design, Andover, MA 01810, USAPassage Bio, Philadelphia, PA 19103, USAAbbvie Bioresearch Center, Worcester, MA 01605, USAAsklepios BioPharmaceuticals, Research Triangle Park, NC 27709, USASpark Therapeutics Inc, Philadelphia, PA 19104, USASpark Therapeutics Inc, Philadelphia, PA 19104, USAAmgen Inc, South San Francisco, CA 94080, USAAbbVie, Irvine, CA 92612, USAVertex Pharmaceuticals, Boston, MA 02210, USABoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USAAstraZeneca, Gothenburg 43250, SwedenRoche Pharma Research and Early Development, Penzberg 82377, GermanyBayer AG, Pharmaceuticals R&D, Berlin 13342, GermanyTakeda Pharmaceuticals International Co, Boston, MA 02139, USABristol Myers Squibb, Lawrence Township, NJ 08648, USAImmunogenicity 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.http://www.sciencedirect.com/science/article/pii/S2329050122001103adeno-associated virusgene therapyimmunogenicityrisk assessmentclinical mitigationbioanalytical methodologies and validation strategies
spellingShingle Tong-yuan Yang
Manuela Braun
Wibke Lembke
Fraser McBlane
John Kamerud
Stephen DeWall
Edit Tarcsa
Xiaodong Fang
Lena Hofer
Uma Kavita
Vijay V. Upreti
Swati Gupta
LiNa Loo
Alison J. Johnson
Rakesh Kantilal Chandode
Kay-Gunnar Stubenrauch
Maya Vinzing
Cindy Q. Xia
Vibha Jawa
Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
Molecular Therapy: Methods & Clinical Development
adeno-associated virus
gene therapy
immunogenicity
risk assessment
clinical mitigation
bioanalytical methodologies and validation strategies
title Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
title_full Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
title_fullStr Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
title_full_unstemmed Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
title_short Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper
title_sort immunogenicity assessment of aav based gene therapies an iq consortium industry white paper
topic adeno-associated virus
gene therapy
immunogenicity
risk assessment
clinical mitigation
bioanalytical methodologies and validation strategies
url http://www.sciencedirect.com/science/article/pii/S2329050122001103
work_keys_str_mv AT tongyuanyang immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT manuelabraun immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT wibkelembke immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT frasermcblane immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT johnkamerud immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT stephendewall immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT edittarcsa immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT xiaodongfang immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT lenahofer immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT umakavita immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT vijayvupreti immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT swatigupta immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT linaloo immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT alisonjjohnson immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT rakeshkantilalchandode immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT kaygunnarstubenrauch immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT mayavinzing immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT cindyqxia immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper
AT vibhajawa immunogenicityassessmentofaavbasedgenetherapiesaniqconsortiumindustrywhitepaper