ArticleJournal of clinical microbiology2009
Use of toll-like receptor assays to detect and identify microbial contaminants in biological products.
Article in Journal of clinical microbiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 67 citations in OpenAlex.
- MDCO-216 Does Not Induce Adverse Immunostimulation, in Contrast to Its Predecessor ETC-216.Cardiovascular drugs and therapy · 2017Trial
- Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes.Journal of leukocyte biology · 2013Trial
- Host cell protein impurities in therapeutic proteins: overview of advances in detection, nonconventional removal technologies and immunogenicity assessment.Journal of biological engineering · 2026Review
- An observational study to test the potency of GLP-grade phenol-free lyophilised leishmanin antigen formulation.EBioMedicine · 2026Article
- Low-dose multi-walled carbon nanotubes are non-inflammatory alone but amplify lipopolysaccharide-induced cytokine responses in A549 lung epithelial spheroids.Frontiers in immunology · 2026Article
- Changes in the Transcriptome and Long Non-Coding RNAs but Not the Methylome Occur in Human Cells Exposed toGenes · 2024Article
- Evaluation of the effect of cell freshness on pyrogen detection using a serum-free monocyte-activation test.PloS one · 2024Article
- Development and Evaluation of a New qPCR Assay for the Detection ofCurrent issues in molecular biology · 2023Article
- A novel approach to evaluate ELISA antibody coverage of host cell proteins-combining ELISA-based immunocapture and mass spectrometry.Biotechnology progress · 2020Article
- Adverse immunostimulation caused by impurities: The dark side of biopharmaceuticals.British journal of clinical pharmacology · 2019Review
- Reporter Cell Assessment of TLR4-Induced NF-κB Responses to Cell-Free Hemoglobin and the Influence of Biliverdin.Biomedicines · 2019Article
- Article
- Use of Toll-like receptor assays for the detection of bacterial contaminations in icodextrin batches released for peritoneal dialysis.Toxicology reports · 2017Article
- High-throughput living cell-based optical biosensor for detection of bacterial lipopolysaccharide (LPS) using a red fluorescent protein reporter system.Scientific reports · 2016Article
- Cobalt ions recruit inflammatory cellsBiochemistry and biophysics reports · 2016Article
- Quantitative definition and monitoring of the host cell protein proteome using iTRAQ - a study of an industrial mAb producing CHO-S cell line.Biotechnology journal · 2016Article
- The future of host cell protein (HCP) identification during process development and manufacturing linked to a risk-based management for their control.Biotechnology and bioengineering · 2015Review
- A repertoire of high-affinity monoclonal antibodies specific to S. typhi: as potential candidate for improved typhoid diagnostic.Immunologic research · 2015Article
- CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling.Oncogene · 2015Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor (TLR)-expressing cells, for the first time, detected and identified a microbial contaminant in a product made in Escherichia coli using an old manufacturing process. It was suspected of having a microbial contaminant(s) because, although it tested negative by standard pyrogen assays, it was associated with adverse events in early clinical trials. The assay readout is the induction of NF-kappaB and/or cytokines in response to TLR activation. Four coded samples, labeled A to D, including a sample prepared by the older manufacturing process, were submitted. The cell lines were activated only by samples B and D. Sample D stimulated only Mono-Mac 6 and HEK-human TLR4 (hTLR4) cells and was later identified as lipopolysaccharide. Except for TLR3 cells, sample B stimulated cells bearing the different TLRs (TLRs 2, 4, 5, 7, 8, and 9) and nontransfected HEK293 cells. These data suggested that flagellin was the microbial contaminant, since TLR5, the receptor for flagellin, is known to be expressed constitutively on HEK293 cells. Moreover, purified flagellin from Salmonella enterica serovar Typhimurium behaved like sample B, stimulating HEK293 and HEK-hTLR5 cells but not HEK-hTLR3 cells, and this stimulation by flagellin and sample B was blocked by an anti-hTLR5 neutralizing antibody. Western blots showed bands positive for flagellin and sample B with the molecular sizes expected for the flagellins from S. Typhimurium and E. coli, respectively. Mass spectrometry data were consistent with the presence of flagellin in the manufacturer's sample B. Taken together, these data indicate that the microbial contaminant in sample B was flagellin and may have been associated with adverse events when the recombinant product was administered.
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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.