ArticlePloS one2017
Quantitative analysis of the CD4+ T cell response to therapeutic antibodies in healthy donors using a novel T cell:PBMC assay.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 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
- Optimisation of in vitro assays for accurate risk assessment of T-cell responses to biologics with potential immune liabilities.Archives of toxicology · 2026Article
- Engineering Fc heterodimerization via asymmetric β-strand reconfiguration for bispecific antibody assembly.Journal of biological engineering · 2026Article
- First step towards predicting clinical immunogenicity of biologics using in vitro based readouts as animal trial alternatives.Journal of pharmaceutical sciences · 2026Article
- Host cell protein impurities in therapeutic proteins: overview of advances in detection, nonconventional removal technologies and immunogenicity assessment.Journal of biological engineering · 2026Review
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- Mechanisms of therapeutic antibodies immunogenicity: infliximab oligomeric aggregates increase T-cell response and uptake by dendritic cells involving mannose-sensitive receptor CD206.Frontiers in immunology · 2026Article
- Immunogenicity Risk Assessment of Biotherapeutics Using an Ex Vivo B Cell Assay.Antibodies (Basel, Switzerland) · 2025Article
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- The preclinical profile of SerpinPC: a potential new treatment for hemophilia.Blood advances · 2025Article
- Generation of frameshift-mutated TGFβR2-specific T cells in healthy subjects following administration with cancer vaccine candidate FMPV-1/GM-CSF in a phase 1 study.Cancer immunology, immunotherapy : CII · 2025Article
- T cell assays for non-clinical immunogenicity risk assessment: best practices recommended by the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Anti-HIV Activity and Immunomodulatory Properties of Fractionated Crude Extracts ofMicroorganisms · 2024Article
- Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Preclinical immunogenicity risk assessment of biotherapeutics using CD4 T cell assays.Frontiers in immunology · 2024Article
- In vivo study of newly developed albumin-conjugated urate oxidase for gout treatment.Arthritis research & therapy · 2023Article
- Effect of O-linked glycosylation on the antigenicity, cellular uptake and trafficking in dendritic cells of recombinant Ber e 1.PloS one · 2021Article
- Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates.Frontiers in immunology · 2020Review
- Specificity of the T Cell Response to Protein Biopharmaceuticals.Frontiers in immunology · 2020Review
- A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro.Vaccines · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many biopharmaceuticals (BPs) are known to be immunogenic in the clinic, which can result in modified pharmacokinetics, reduced efficacy, allergic reactions and anaphylaxis. During recent years, several technologies to predict immunogenicity have been introduced, but the predictive value is still considered low. Thus, there is an unmet medical need for optimization of such technologies. The generation of T cell dependent high affinity anti-drug antibodies plays a key role in clinical immunogenicity. This study aimed at developing and evaluating a novel in vitro T cell:PBMC assay for prediction of the immunogenicity potential of BPs. To this end, we assessed the ability of infliximab (anti-TNF-α), rituximab (anti-CD20), adalimumab (anti-TNF-α) and natalizumab (anti-α4-integrin), all showing immunogenicity in the clinic, to induce a CD4+ T cells response. Keyhole limpet hemocyanin (KLH) and cytomegalovirus pp65 protein (CMV) were included as neo-antigen and recall antigen positive controls, respectively. By analyzing 26 healthy donors having HLA-DRB1 alleles matching the European population, we calculated the frequency of responding donors, the magnitude of the response, and the frequency of BP-specific T cells, as measured by 3[H]-thymidine incorporation and ELISpot IL-2 secretion. KLH and CMV demonstrated a strong T cell response in all the donors analyzed. The frequency of responding donors to the BPs was 4% for infliximab, 8% for adalimumab, 19% for rituximab and 27% for natalizumab, which is compared to and discussed with their respective observed clinical immunogenicity. This study further complements predictive immunogenicity testing by quantifying the in vitro CD4+ T cell responses to different BPs. Even though the data generated using this modified method does not directly translate to the clinical situation, a high sensitivity and immunogenic potential of most BPs is demonstrated.
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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.