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...
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Format: | Article |
Language: | English |
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Elsevier
2022-09-01
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Series: | Molecular Therapy: Methods & Clinical Development |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050122001103 |
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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 |
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