ArticlePharmaceutical research2015
The immunogenicity of antibody aggregates in a novel transgenic mouse model.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 122 citations in OpenAlex.
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- Insights into Photo Degradation and Stabilization Strategies of Antibody-Drug Conjugates with Camptothecin Payloads.Pharmaceutics · 2025Article
- Application of humanized mice in the safety experiments of antibody drugs.Animal models and experimental medicine · 2025Review
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- Preclinical B cell depletion and safety profile of a brain-shuttled crystallizable fragment-silenced CD20 antibody.Clinical and translational medicine · 2025Article
- MAPPs assays for non-clinical immunogenicity risk assessment: best practices recommended by the European immunogenicity platform.Frontiers in immunology · 2025Review
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
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- A High Threshold of Biotherapeutic Aggregate Numbers is Needed to Induce an Immunogenic Response In Vitro, In Vivo, and in the Clinic.Pharmaceutical research · 2024Article
- Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates.Pharmaceutics · 2022Review
- A humanized minipig model for the toxicological testing of therapeutic recombinant antibodies.Nature biomedical engineering · 2022Article
- Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis.International journal of molecular sciences · 2022Article
- Image Analysis Algorithm-Based Platform for Determining Micron and Higher Aggregate Size Distribution of Therapeutic IgG Using Brightfield and Fluorescence Microscope Images.Pharmaceutical research · 2021Article
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods.International journal of molecular sciences · 2021Article
- Pharmaceutical Excipients Enhance Iron-Dependent Photo-Degradation in Pharmaceutical Buffers by near UV and Visible Light: Tyrosine Modification by Reactions of the Antioxidant Methionine in Citrate Buffer.Pharmaceutical research · 2021Article
- Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis.International journal of molecular sciences · 2020Article
- Protein aggregation and immunogenicity of biotherapeutics.International journal of pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeProtein aggregates have been discussed as a potential risk factor related to immunogenicity. Here we developed a novel human IgG transgenic (tg) mouse system expressing a mini-repertoire of human IgG1 antibodies (Abs) for the assessment of immunogenic properties of human mAb preparations.
methodsTransgenic mice were generated using germline versions of the human Ig heavy chain γ1 (IgH-γ1), and the human Ig light chain (IgL) κ and λ genes. Only the soluble form of human IgH-γ1 was used to avoid expression of the membrane Ig-H chain and concomitant allelic exclusion of endogenous murine Ig genes. IgG1 aggregates were generated by different stress conditions such as process-related, low pH and exposure to artificial light.
resultsThe expression of human Ig proteins induced immunological tolerance to a broad range of human IgG1 molecules in the tg mice. Immunization with IgG1 aggregates demonstrated that soluble oligomers induced by significant light-exposure and carrying neo-epitopes induced a strong immune response in tg mice. In contrast, Ab aggregates alone and monomers with neo-epitopes were not immunogenic.
conclusionThis mouse model is able to recognize immunogenic modifications of human IgG1. While the degree of stress-induced aggregation varies for different mAbs, our findings using a particular mAb (mAb1) demonstrate that non-covalently modified aggregates do not break tolerance, contrary to widely held opinion. The immunogenic potential of soluble aggregates of human IgG strongly depends on the presence of neo-epitopes resulting from harsh stress conditions, i.e. extensive exposure to artificial light.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.