Molecular Landscape of Anti-Drug Antibodies Reveals the Mechanism of the Immune Response Following Treatment With TNFα Antagonists.
anti-drug antibodies
antibody repertoire
biologics
high-throughput sequencing
immunogenicity
monoclonal antibody
next generation sequencing
proteomics
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2019
2019
Historique:
received:
16
09
2019
accepted:
28
11
2019
entrez:
11
1
2020
pubmed:
11
1
2020
medline:
11
11
2020
Statut:
epublish
Résumé
Drugs formulated from monoclonal antibodies (mAbs) are clinically effective in various diseases. Repeated administration of mAbs, however, elicits an immune response in the form of anti-drug-antibodies (ADA), thereby reducing the drug's efficacy. Notwithstanding their importance, the molecular landscape of ADA and the mechanisms involved in their formation are not fully understood. Using a newly developed quantitative bio-immunoassay, we found that ADA concentrations specific to TNFα antagonists can exceed extreme concentrations of 1 mg/ml with a wide range of neutralization capacity. Our data further suggest a preferential use of the λ light chain in a subset of neutralizing ADA. Moreover, we show that administration of TNFα antagonists result in a vaccine-like response whereby ADA formation is governed by the extrafollicular T cell-independent immune response. Our bio-immunoassay coupled with insights on the nature of the immune response can be leveraged to improve mAb immunogenicity assessment and facilitate improvement in therapeutic intervention strategies.
Identifiants
pubmed: 31921180
doi: 10.3389/fimmu.2019.02921
pmc: PMC6930160
doi:
Substances chimiques
Antibodies, Monoclonal
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2921Informations de copyright
Copyright © 2019 Vaisman-Mentesh, Rosenstein, Yavzori, Dror, Fudim, Ungar, Kopylov, Picard, Kigel, Ben-Horin, Benhar and Wine.
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