ArticleThe Journal of biological chemistry2012
Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it.
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Multimodal Anion-Exchange Resins for Chromatographic Separation of Antibody Aggregates.Biomolecules · 2026Article
- Preclinical Pharmacokinetic, Pharmacodynamic, and Safety Profile of OBI-992: A Novel TROP2-Targeted Antibody-Drug Conjugate.Molecular cancer therapeutics · 2025Article
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- Inhalative polyclonal immunoglobulin G for the prevention of respiratory infections: A comprehensiveInternational journal of pharmaceutics: X · 2025Article
- Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems.Pharmaceutical research · 2025Article
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- Impact of Monoclonal Antibody Aggregates on Effector Function Characterization.Antibodies (Basel, Switzerland) · 2025Article
- Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy.Scientific reports · 2025Article
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- Impact of Weak Vibration Generated by a Refrigerator on Protein Aggregation.The AAPS journal · 2025Article
- Dendritic cell maturation assay 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
- 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
- Taurine, a Naturally Occurring Amino Acid, as a Physical Stability Enhancer of Different Monoclonal Antibodies.The AAPS journal · 2024Article
- Enhancing thermal stability in the CHProtein science : a publication of the Protein Society · 2023Article
- Getting Smaller by Denaturation: Acid-Induced Compaction of Antibodies.The journal of physical chemistry letters · 2023Article
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of biotherapeutics has the potential to induce an immunogenic response. Here, we show that aggregated therapeutic antibodies, previously generated and determined to contain a variety of attributes (Joubert, M. K., Luo, Q., Nashed-Samuel, Y., Wypych, J., and Narhi, L. O. (2011) J. Biol. Chem. 286, 25118-25133), can enhance the in vitro innate immune response of a population of naive human peripheral blood mononuclear cells. This response depended on the aggregate type, inherent immunogenicity of the monomer, and donor responsiveness, and required a high number of particles, well above that detected in marketed drug products, at least in this in vitro system. We propose a cytokine signature as a potential biomarker of the in vitro peripheral blood mononuclear cell response to aggregates. The cytokines include IL-1β, IL-6, IL-10, MCP-1, MIP-1α, MIP-1β, MMP-2, and TNF-α. IL-6 and IL-10 might have an immunosuppressive effect on the long term immune response. Aggregates made by stirring induced the highest response compared with aggregates made by other methods. Particle size in the 2-10 μm range and the retention of some folded structure were associated with an increased response. The mechanism of aggregate activation at the innate phase was found to occur through specific cell surface receptors (the toll-like receptors TLR-2 and TLR-4, FcγRs, and the complement system). The innate signal was shown to progress to an adaptive T-cell response characterized by T-cell proliferation and secretion of T-cell cytokines. Investigating the ability of aggregates to induce cytokine signatures as biomarkers of immune responses is essential for determining their risk of immunogenicity.
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