ArticleFrontiers in immunology2023
The immunogenicity of human-origin therapeutic antibodies are associated with V gene usage.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Characterization of the VHH-Fc construct rimteravimab in healthy adults and patients hospitalized for mild-to-moderate COVID-19: Two Phase 1 randomized clinical trials.PLoS medicine · 2026Trial
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- Long-term depletion of KIR3DL01+ NK cells by adeno-associated viral-vectored antibody delivery alters chronic SIV infection.PLoS pathogens · 2026Article
- Fully Humanized Bispecific T Cell Engager Shows Potent Activity in Central Nervous System and Peripheral Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phage Display Technology: Design, Library Construction, and Panning Strategies for Antibody Development.Biomolecules & therapeutics · 2026Review
- The immunogenicity database collaborative: a standardized, publicly available database for clinical immunogenicity observations and insights.Frontiers in immunology · 2026Article
- Fitness Landscape for Antibodies 2: Benchmarking Reveals That Protein AI Models Cannot Yet Consistently Predict Developability Properties.bioRxiv : the preprint server for biology · 2025Article
- Nanotechnology Approaches for Mitigating Biologic Immunogenicity: A Literature Review.Pharmaceutics · 2025Review
- Anti-Drug Antibody Response to Therapeutic Antibodies and Potential Mitigation Strategies.Biomedicines · 2025Review
- Evaluating the Immunogenicity Risk of Protein Therapeutics by Augmenting T Cell Epitope Prediction with Clinical Factors.The AAPS journal · 2025Article
- Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.Antibodies (Basel, Switzerland) · 2024Article
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Authors and funding
3 authors.
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Abstract
Therapeutic antibodies can elicit unwanted immune responses in a subset of patients, which leads to the production of anti-drug antibodies (ADA). Some of these ADAs have been reported to effect the pharmacokinetics, efficacy and/or safety of the therapeutic antibodies. The sequence diversity of antibodies are generated by VDJ recombination and mutagenesis. While the antibody generation process can create a large candidate pool for identifying high-affinity antibodies, it also could produce sequences that are foreign to the human immune system. However, it is not clear how VDJ recombination and mutagenesis impact the clinical ADA rate of therapeutic antibodies. In this study, we identified a positive correlation between the clinical ADA rate and the number of introduced mutations in the antibody sequences. We also found that the use of rare V alleles in human-origin antibody therapeutics is associated with higher risk of immunogenicity. The results suggest that antibody engineering projects should start with frameworks that contain commonly used V alleles and prioritize antibody candidates with low number of mutations to reduce the risk of immunogenicity.
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