ArticleBlood advances2017
T-cell assays confirm immunogenicity of tungsten-induced erythropoietin aggregates associated with pure red cell aplasia.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 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
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Preventive Pharmacovigilance: timely and precise prevention of adverse events through person-level patient screening and dose-level product surveillance.Pharmaceutical research · 2023Article
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- Isotropic conductive paste for bioresorbable electronics.Materials today. Bio · 2023Article
- An Institutional Guide for Formulary Decisions of Biosimilars.Hospital pharmacy · 2023Review
- Immunogenicity Risk Assessment of Spontaneously Occurring Therapeutic Monoclonal Antibody Aggregates.Frontiers in immunology · 2022Article
- All vials are not the same: Potential role of vaccine quality in vaccine adverse reactions.Vaccine · 2021Article
- Modified recombinant human erythropoietin with potentially reduced immunogenicity.Scientific reports · 2021Article
- The Path Towards a Tailored Clinical Biosimilar Development.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- Immunogenicity Risk Assessment for an Engineered Human Cytokine Analogue Expressed in Different Cell Substrates.The AAPS journal · 2020Review
- Specificity of the T Cell Response to Protein Biopharmaceuticals.Frontiers in immunology · 2020Review
- Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates.Frontiers in immunology · 2020Review
- TCPro: an In Silico Risk Assessment Tool for Biotherapeutic Protein Immunogenicity.The AAPS journal · 2019Article
- Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019Review
- Epoetin Biosimilars in the Treatment of Renal Anemia: What Have We Learned from a Decade of European Experience?Clinical drug investigation · 2018Article
- HX575: established biosimilarity in the treatment of renal anemia and 10 years of clinical experience.Drug design, development and therapy · 2018Review
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunogenicity of biotherapeutics and the elicitation of anti-drug antibodies are a key concern for their efficacy, pharmacokinetics, and safety. A particularly severe consequence of immunogenicity of a biotherapeutic is the rare development of antibody-mediated pure red cell aplasia (PRCA) in anemic patients treated with aggregated forms of recombinant human erythropoietin (rhEPO). Here, we investigated in vitro T-cell responses to experimentally heat-induced rhEPO aggregates, and to tungsten-induced rhEPO aggregates in clinical lots associated with rhEPO-neutralizing antibodies and PRCA. Heat-stressed rhEPO elicited T-cell responses only in blood obtained from healthy individuals identified as responders, whereas nonstressed rhEPO overall did not induce reactions neither in responders nor nonresponders. Tungsten-induced rhEPO aggregates in clinical lots associated with rhEPO-neutralizing antibodies and PRCA could induce in vitro T-cell responses in blood obtained from healthy donors, in contrast to rhEPO from low tungsten syringes. Importantly, ex vivo T-cell recall responses of patients treated with rhEPO without PRCA showed no T-cell responses, whereas T cells of a patient who developed PRCA after treatment with a clinical batch with elevated levels of tungsten and rhEPO aggregates showed a clear response to rhEPO from that clinical batch. To our knowledge, this is the first time that T-cell assays confirm the root cause of increased rhEPO immunogenicity associated with PRCA.
Identifiers
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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.