ArticlemAbs2019
Investigation of pre-existing reactivity to biotherapeutics can uncover potential immunogenic epitopes and predict immunogenicity risk.
Article in mAbs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.Blood advances · 2021Trial
- Rethinking immunogenicity: an integrated approach reveals the PK/PD impact of pre-existing and drug-sustaining ADA.Bioanalysis · 2026Article
- Generation of Bispecific Antibodies Using FAST-Ig™.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Review of the Existing Translational Pharmacokinetics Modeling Approaches Specific to Monoclonal Antibodies (mAbs) to Support the First-In-Human (FIH) Dose Selection.International journal of molecular sciences · 2022Review
- Immunogenicity assessment of bispecific antibody-based immunotherapy in oncology.Journal for immunotherapy of cancer · 2022Review
- Conduit CAR: Redirecting CAR T-Cell Specificity with A Universal and Adaptable Bispecific Antibody Platform.Cancer research communications · 2022Article
- Bioanalysis in the Age of New Drug Modalities.The AAPS journal · 2021Review
- Immunogenicity of biologic agents in rheumatology.Nature reviews. Rheumatology · 2021Review
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Neutralization Breadth and Potency of Single-Chain Variable Fragments Derived from Broadly Neutralizing Antibodies Targeting Multiple Epitopes on the HIV-1 Envelope.Journal of virology · 2020Article
- Correlation between antidrug antibodies, pre-existing antidrug reactivity, and immunogenetics (MHC class II alleles) in cynomolgus macaque.Immunogenetics · 2019Article
- Review
- Article
- Design of antibody variable fragments with reduced reactivity to preexisting anti-drug antibodies.mAbsArticle
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent advances in the development of tools to predict immunogenicity risk of biotherapeutic molecules, the ability of a protein to elicit the formation of anti-drug antibodies (ADA) remains one of the most common causes for termination of clinical development programs. In this study, we use ADA assays to detect and measure pre-existing reactivity or the ability of a molecule to produce an ADA-like response in serum from treatment-naïve, healthy donors. We report herein that the magnitude of pre-existing reactivity evaluated pre-clinically and expressed as the 90th percentile of Tier 2 inhibition correlates with the subsequent rate of ADA emergence in the clinic. Furthermore, a multi-domain biotherapeutic (IgG-scFv bispecific antibody) showed the highest pre-existing reactivity and incidence of treatment-emergent ADA (TE-ADA) (57% and 93%, respectively). Using the components of the multidomain molecule in the Tier 2 step of the ADA assay, we were able to identify the scFv as the target of the serum pre-existing reactivity. Most importantly, the domain specificity of pre-existing ADA was the same as that of the TE-ADA from patients treated with the molecule. Based on these data, we propose the evaluation of the magnitude and of the domain specificity of pre-existing reactivity as a powerful tool to understand the immunogenic potential of novel biotherapeutics.
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