ArticlePharmaceutical research2015
Small amounts of sub-visible aggregates enhance the immunogenic potential of monoclonal antibody therapeutics.
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 72 papers.
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Who cites it
72 citing papers in PubMed, 166 citations in OpenAlex.
- Separation of Monoclonal Antibody Aggregates Using an Analytical Ultrafiltration Technique.Membranes · 2026Article
- Modulation of Intravenous Immunoglobulin Aggregation, Subvisible Particle Formation, and Viscosity by Acetylated Amino Acids.Pharmaceutics · 2026Article
- Review
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- Development and practical validation of BUBBLESS tapping instrument for efficient bubble removal during antibody drug mixing.Journal of pharmaceutical health care and sciences · 2026Article
- Incidence and implications of anti-rituximab antibodies in nephropathies and other immune-mediated diseases: a narrative review.Frontiers in immunology · 2026Review
- Mechanisms of therapeutic antibodies immunogenicity: infliximab oligomeric aggregates increase T-cell response and uptake by dendritic cells involving mannose-sensitive receptor CD206.Frontiers in immunology · 2026Article
- Inhalative polyclonal immunoglobulin G for the prevention of respiratory infections: A comprehensiveInternational journal of pharmaceutics: X · 2025Article
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- Unraveling the Effects of Filtration, Process Interruptions, and Post-Process Agitation on Protein Aggregation.AAPS PharmSciTech · 2025Article
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- A real-time imaging approach to quantify dendritic cell internalization for immunogenicity risk assessment of biotherapeutics.Frontiers in immunology · 2025Article
- Antigen-presenting cell internalization is key for understanding and evaluating therapeutic antibodies' immunogenicity.Frontiers in immunology · 2025Review
- Advancements in research and clinical management of interstitial lung injury associated with ADC drugs administration in breast cancer.Discover oncology · 2024Review
- Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- 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
- Development and Validation of a Cell-Based Binding Neutralizing Antibody Assay for an Antibody-Drug Conjugate.The AAPS journal · 2024Article
- Development and characterization of dendritic cell internalization and activation assays contributing to the immunogenicity risk evaluation of biotherapeutics.Frontiers in immunology · 2024Article
- Stabilization challenges and aggregation in protein-based therapeutics in the pharmaceutical industry.RSC advances · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDetermine the effect of minute quantities of sub-visible aggregates on the in vitro immunogenicity of clinically relevant protein therapeutics.
methodsMonoclonal chimeric (rituximab) and humanized (trastuzumab) antibodies were subjected to fine-tuned stress conditions to achieve low levels (<3% of total protein) of sub-visible aggregates. The effect of stimulating human dendritic cells (DC) and CD4(+) T cells with the aggregates was measured in vitro using cytokine secretion, proliferation and confocal microscopy.
resultsDue to its intrinsic high clinical immunogenicity, aggregation of rituximab had minimal effects on DC activation and T cell responses compared to monomeric rituximab. However, in the case of trastuzumab (low clinical immunogenicity) small quantities of aggregates led to potent CD4(+) T cell proliferation as a result of strong cytokine and co-stimulatory signals derived from DC. Consistent with this, confocal studies showed that stir-stressed rituximab was rapidly internalised and associated with late endosomes of DC.
conclusionsThese data link minute amounts of aggregates with activation of the innate immune response, involving DC, resulting in T cell activation. Thus, when protein therapeutics with little or no clinical immunogenicity, such as trastuzumab, contain minute amounts of sub-visible aggregates, they are associated with significantly increased potential risk of clinical immunogenicity.
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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.