ArticlePloS one2010
Trace levels of innate immune response modulating impurities (IIRMIs) synergize to break tolerance to therapeutic proteins.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results.Clinical ophthalmology (Auckland, N.Z.) · 2023Trial
- Multiplexed Immunophenotyping for Innate Activation Assessment Detects Single-Cell Responses to Immunomodulatory Nucleic Acid Impurities in Therapeutics.The AAPS journal · 2026Article
- Cellular Immunogenicity Assessments in CAR-T Cell Therapies: Current Insights and Future Directions.The AAPS journal · 2025Article
- Cell-Based Assays to Detect Innate Immune Response Modulating Impurities: Application to Biosimilar Insulin.The AAPS journal · 2024Article
- Assessing MAPPs assay as a tool to predict the immunogenicity potential of protein therapeutics.Life science alliance · 2024Article
- Detection of innate immune response modulating impurities (IIRMI) in therapeutic peptides and proteins: Impact of excipients.Frontiers in immunology · 2022Article
- Assessment of innate immune response modulating impurities in glucagon for injection.PloS one · 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
- Innate Immunity Modulating Impurities and the Immunotoxicity of Nanobiotechnology-Based Drug Products.Molecules (Basel, Switzerland) · 2021Review
- The expression and activity of Toll-like receptors in the preimplantation human embryo suggest a new role for innate immunity.Human reproduction (Oxford, England) · 2021Article
- Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- A Highly Sensitive Cell-Based TLR Reporter Platform for the Specific Detection of Bacterial TLR Ligands.Frontiers in immunology · 2021Article
- Immunogenicity Risk Assessment for an Engineered Human Cytokine Analogue Expressed in Different Cell Substrates.The AAPS journal · 2020Review
- CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis.PLoS neglected tropical diseases · 2020Article
- Specificity of the T Cell Response to Protein Biopharmaceuticals.Frontiers in immunology · 2020Review
- Multiplexed Gene Expression as a Characterization of Bioactivity for Interferon Beta (IFN-β) Biosimilar Candidates: Impact of Innate Immune Response Modulating Impurities (IIRMIs).The AAPS journal · 2019Article
- Lipopolysaccharides in Food, Food Supplements, and Probiotics: Should We be Worried?European journal of microbiology & immunology · 2018Review
- Aggregates of IVIG or Avastin, but not HSA, modify the response to model innate immune response modulating impurities.Scientific reports · 2018Article
- Advancements in Understanding Immunogenicity of Biotherapeutics in the Intraocular Space.The AAPS journal · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs) that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS) and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st) dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.
Indexed as
Identifiers
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.