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- Title
Molecular Landscape of Anti-Drug Antibodies Reveals the Mechanism of the Immune Response Following Treatment With TNFα Antagonists.
- Authors
Vaisman-Mentesh, Anna; Rosenstein, Shai; Yavzori, Miri; Dror, Yael; Fudim, Ella; Ungar, Bella; Kopylov, Uri; Picard, Orit; Kigel, Aya; Ben-Horin, Shomron; Benhar, Itai; Wine, Yariv
- 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.
- Subjects
IMMUNE response; MONOCLONAL antibodies; IMMUNOGLOBULINS; DRUG efficacy
- Publication
Frontiers in Immunology, 2019, Vol 10, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2019.02921