ReviewJournal of immunotoxicology
Immunogenicity of therapeutic proteins: influence of aggregation.
Review in Journal of immunotoxicology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
207 citing papers in PubMed, 1 synthesis or guideline pooled it, 564 citations in OpenAlex.
- Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes.Drugs · 2018Pooled it
- The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate.Rheumatology (Oxford, England) · 2023Trial
- Article
- Lipid-Based Delivery Systems for Therapeutic Glycoproteins: Current Advances, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- From anti-drug antibody incidence to clinical relevance: interpreting highly sensitive immunogenicity assays in biosimilars.Bioanalysis · 2026Article
- Predicting Agitation Stability of Monoclonal Antibodies during Developability Assessment.Molecular pharmaceutics · 2026Article
- Recent Advances in Particle Design for High-Concentration Protein Suspension Injectables.Pharmaceutics · 2026Review
- Incidence and implications of anti-rituximab antibodies in nephropathies and other immune-mediated diseases: a narrative review.Frontiers in immunology · 2026Review
- Artificial intelligence advancements in monoclonal antibody development technology.Frontiers in immunology · 2026Review
- A Deletion Variant of Human Factor VIII Displaying Low Immunogenicity in a Murine Model of Hemophilia A.International journal of molecular sciences · 2025Article
- Advanced cell-derived drug delivery systems for pulmonary diseases: from bench to bedside.Drug delivery · 2025Review
- Inhalative polyclonal immunoglobulin G for the prevention of respiratory infections: A comprehensiveInternational journal of pharmaceutics: X · 2025Article
- Article
- From Pathology to Materials Science and Engineering: Harnessing the Amyloid State for Biotechnological Applications.ACS applied materials & interfaces · 2025Review
- Two novel conserved linear B-cell epitopes identified in the S2 subunit of the infectious bronchitis virus spike protein.Virus research · 2025Article
- Effect of a smart temperature logger on correctly storing biological disease-modifying antirheumatic drugs at home: a pre-post study.European journal of hospital pharmacy : science and practice · 2025Article
- Peptide Mapping for Sequence Confirmation of Therapeutic Proteins and Recombinant Vaccine Antigens by High-Resolution Mass Spectrometry: Software Limitations, Pitfalls, and Lessons Learned.International journal of molecular sciences · 2025Article
- Characterizing Monoclonal Antibody Aggregation Using Charge Detection Mass Spectrometry and Industry Standard Methods.Journal of the American Society for Mass Spectrometry · 2025Article
- SITA: Predicting site-specific immunogenicity for therapeutic antibodies.Journal of pharmaceutical analysis · 2025Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The elicitation of anti-drug antibodies (ADA) against biotherapeutics can have detrimental effects on drug safety, efficacy, and pharmacokinetics. The immunogenicity of biotherapeutics is, therefore, an important issue. There is evidence that protein aggregation can result in enhanced immunogenicity; however, the precise immunological and biochemical mechanisms responsible are poorly defined. In the context of biotherapeutic drug development and safety assessment, understanding the mechanisms underlying aggregate immunogenicity is of considerable interest. This review provides an overview of the phenomenon of protein aggregation, the production of unwanted aggregates during bioprocessing, and how the immune response to aggregated protein differs from that provoked by non-aggregated protein. Of particular interest is the nature of the interaction of aggregates with the immune system and how subsequent ADA responses are induced. Pathways considered here include 'classical' activation of the immune system involving antigen presenting cells and, alternatively, the breakdown of B-cell tolerance. Additionally, methods available to screen for aggregation and immunogenicity will be described. With an increased understanding of aggregation-enhanced immune responses, it may be possible to develop improved manufacturing and screening processes to avoid, or at least reduce, the problems associated with ADA.
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What OpenQuestion holds
Registered trials
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.