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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
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 Ydoi
10.3389/fimmu.2019.02921subject
Has Abstractpub_date
2019-12-18 00:00:00pages
2921issn
1664-3224journal_volume
10pub_type
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