Binding and neutralizing anti-AAV antibodies: Detection and implications for rAAV-mediated gene therapy.
efficacy
gene therapy
humoral immunity
neutralizing antibodies
recombinant adeno-associated virus
safety
seroprevalence
total antibody assay
transduction inhibition assay
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
received:
11
10
2022
revised:
21
12
2022
accepted:
06
01
2023
pmc-release:
01
03
2024
pubmed:
14
1
2023
medline:
7
3
2023
entrez:
13
1
2023
Statut:
ppublish
Résumé
Assessment of anti-adeno-associated virus (AAV) antibodies in patients prior to systemic gene therapy administration is an important consideration regarding efficacy and safety of the therapy. Approximately 30%-60% of individuals have pre-existing anti-AAV antibodies. Seroprevalence is impacted by multiple factors, including geography, age, capsid serotype, and assay type. Anti-AAV antibody assays typically measure (1) transduction inhibition by detecting the neutralizing capacity of antibodies and non-antibody neutralizing factors, or (2) total anti-capsid binding antibodies, regardless of neutralizing activity. Presently, there is a paucity of head-to-head data and standardized approaches associating assay results with clinical outcomes. In addition, establishing clinically relevant screening titer cutoffs is complex. Thus, meaningful comparisons across assays are nearly impossible. Although complex, establishing screening assays in routine clinical practice to identify patients with antibody levels that may impact favorable treatment outcomes is achievable for both transduction inhibition and total antibody assays. Formal regulatory approval of such assays as companion diagnostic tests will confirm their suitability for specific recombinant AAV gene therapies. This review covers current approaches to measure anti-AAV antibodies in patient plasma or serum, their potential impact on therapeutic safety and efficacy, and investigative strategies to mitigate the effects of pre-existing anti-AAV antibodies in patients.
Identifiants
pubmed: 36635967
pii: S1525-0016(23)00010-2
doi: 10.1016/j.ymthe.2023.01.010
pmc: PMC10014285
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Capsid Proteins
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
616-630Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests S.H.C., M.S., S.S., G.B., I.W., M.M., and D.L. are employees of Pfizer. C.J.P. is an employee of Labcorp-Monogram Biosciences.
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