Molecular landscape of anti-drug antibodies reveals the mechanism of the immune response following treatment with TNFα antagonists
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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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Immunogenicity negatively affects therapeutic efficacy and impacts safety through the induction of adverse drug reactions.
“Immunogenicity negatively affects therapeutic efficacy and impacts safety through the induction of adverse drug reactions [30].”
From Computational and artificial intelligence-based methods for antibody development (2023) · cites this paper as [30]
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- [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
- Publisher
- Frontiers Media SA
- Published
- 2019-12-18
- Volume
- 10
- Pages
- 2921-2921
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6930160
- 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
- gold
- doi.org
- Licence
- 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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