Cited by 54Monoclonal and Polyclonal Antibodies ResearchBiosimilars and Bioanalytical MethodsSystemic Lupus Erythematosus Research

Molecular landscape of anti-drug antibodies reveals the mechanism of the immune response following treatment with TNFα antagonists

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Vaisman-Mentesh, Anna, Rosenstein, Shai, Yavzori, Miri, Dror, Yael, Fudim, Ella, Ungar, Bella, Kopylov, Uri, Picard, Orit +4 more·2019·Frontiers in Immunology

Published version of a preprint

Abstract

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.

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  1. [54]Vaisman-Mentesh V Rosenstein S Yavzori M Dror Y Fudim E Ungar B Molecular landscape of anti-drug antibodies reveals the mechanism of the immune response following treatment with TNFα antagonists. biorxiv. (2019). 10.1101/509489 PMC6930160 31921180 · DOI

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Authors
Vaisman-Mentesh, A., Rosenstein, S., Yavzori, M., Dror, Y., Fudim, E., Ungar, B., Kopylov, U., Picard, O., Kigel, A., Ben-Horin, S., Benhar, I., & Wine, Y.
Affiliations
Tel Aviv University (IL)
Corresponding author
Wine, Yariv
Venue
Frontiers in Immunology
Published
2019-12-18
Volume
10
Pages
2921-2921
ISSN
1664-3224 (ISSN-L)
OpenAlex
W2991056046
Cited by
54
References
54
Citations by year
2026: 2 · 2025: 4 · 2024: 9 · 2023: 5 · 2022: 12 · 2021: 12 · 2020: 7 · 2019: 2 · 2018: 1
FWCI
5.45
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
University of Texas at Austin
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords
anti-drug antibodies, monoclonal antibodies, immunogenicity, antibody neutralization, lambda light chain, T cell-independent immune response, extrafollicular B cells
MeSH terms
Antibodies, Monoclonal, Humans, Immunoassay, Tumor Necrosis Factor-alpha

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