ArticleScientific reports2018
Aggregates of IVIG or Avastin, but not HSA, modify the response to model innate immune response modulating impurities.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 33 citations in OpenAlex.
- Synovial MS4A4A correlates with inflammation and counteracts response to corticosteroids in arthritis.Proceedings of the National Academy of Sciences of the United States of America · 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
- Cell-Based Assays to Detect Innate Immune Response Modulating Impurities: Application to Biosimilar Insulin.The AAPS journal · 2024Article
- Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.Cellular and molecular life sciences : CMLS · 2024Article
- Amyloid-like RIP1/RIP3 RHIM Fragments' Characterization and Application as a Drug Depot.Molecules (Basel, Switzerland) · 2023Article
- Fcγ Receptor-Dependent Internalization and Off-Target Cytotoxicity of Antibody-Drug Conjugate Aggregates.Pharmaceutical research · 2022Article
- Detection of innate immune response modulating impurities (IIRMI) in therapeutic peptides and proteins: Impact of excipients.Frontiers in immunology · 2022Article
- An In Vitro Assessment of Immunostimulatory Responses to Ten Model Innate Immune Response Modulating Impurities (IIRMIs) and Peptide Drug Product, Teriparatide.Molecules (Basel, Switzerland) · 2021Article
- Lessons Learned in Protein Precipitation Using a Membrane Emulsification Technique to Produce Reversible and Uniform Microbeads.Pharmaceutics · 2021Article
- Severe Thrombocytopenia in a Case of Epstein-Barr Virus-Induced Infectious Mononucleosis.Cureus · 2021Article
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic proteins can induce immune responses that affect their safety and efficacy. Product aggregates and innate immune response modulating impurities (IIRMI) are risk factors of product immunogenicity. In this study, we use Intravenous Immunoglobulin (IVIG), Avastin, and Human Serum Albumin (HSA) to explore whether increased aggregates activate innate immune cells or modify the response to IIRMI. We show that increased aggregates (shaken or stirred) in IVIG and Avastin, but not HSA, induced activation of MAPKs (pp38, pERK and pJNK) and transcription of immune-related genes including IL8, IL6, IL1β, CSF1, CCL2, CCL7, CCL3, CCL24, CXCL2, IRAK1, EGR2, CEBPβ, PPARg and TNFSF15 in human PBMC. The immunomodulatory effect was primarily mediated by FcγR, but not by TLR. Interestingly, increased aggregates in IVIG or Avastin magnified innate immune responses to TLR2/4 agonists, but diminished responses to TLR3/9 agonists. This study shows that IIRMI and aggregates can modify the activity of immune cells potentially modifying the milieu where the products are delivered highlighting the complex interplay of different impurities on product immunogenicity risk. Further, we show that aggregates could modify the sensitivity of PBMC-based assays designed to detect IIRMI. Understanding and managing immunogenicity risk is a critical component of product development and regulation.
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