ArticleClinical and experimental immunology2016
Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody.
Article in Clinical and experimental immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 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
- Safety, pharmacokinetics and pharmacodynamics of BI 655064 in phase 1 clinical trials in healthy Chinese and Japanese subjects.British journal of clinical pharmacology · 2021Trial
- Trial
- Optimisation of in vitro assays for accurate risk assessment of T-cell responses to biologics with potential immune liabilities.Archives of toxicology · 2026Article
- Review
- A universal monoallelic human leukocyte antigen class II immunopeptidomic platform for defining the immunogenicity potential of therapeutic proteins.Communications biology · 2025Article
- Disentangling effects of the DR and DQ isomers encoded by the HLA class II haplotype DRB1*15:01/DQB1*06:02 to help establish the true risk allele for FVIII inhibitor development in Hemophilia A.Frontiers in genetics · 2025Article
- A real-time imaging approach to quantify dendritic cell internalization for immunogenicity risk assessment of biotherapeutics.Frontiers in immunology · 2025Article
- Antigen-presenting cell internalization is key for understanding and evaluating therapeutic antibodies' immunogenicity.Frontiers in immunology · 2025Review
- Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Dendritic cell maturation assay for non-clinical immunogenicity risk assessment: best practices recommended by the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- T cell assays for non-clinical immunogenicity risk assessment: best practices recommended by the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- The effects of interleukin-21 in the biology of transplant rejection.Frontiers in immunology · 2025Review
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- FASTMAP-a flexible and scalable immunopeptidomics pipeline for HLA- and antigen-specific T-cell epitope mapping based on artificial antigen-presenting cells.Frontiers in immunology · 2024Article
- Development and characterization of dendritic cell internalization and activation assays contributing to the immunogenicity risk evaluation of biotherapeutics.Frontiers in immunology · 2024Article
- A mechanistic marker-based screening tool to predict clinical immunogenicity of biologics.Communications medicine · 2023Article
- Survey Outcome on Immunogenicity Risk Assessment Tools for Biotherapeutics: an Insight into Consensus on Methods, Application, and Utility in Drug Development.The AAPS journal · 2023Article
- Development of a semi-automated MHC-associated peptide proteomics (MAPPs) method using streptavidin bead-based immunoaffinity capture and nano LC-MS/MS to support immunogenicity risk assessment in drug development.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR-107 [anti-interleukin (IL)-21 receptor] that elicited anti-drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR-107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL-21R on DCs, ATR-107 did not bind to the DCs more extensively than the control therapeutic antibody (PF-1) that had elicited low clinical ADA incidence. However, ATR-107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co-localized with intracellular antigen-D related (HLA-DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR-107 induced increased DC activation exemplified by up-regulation of DC surface expression of CD86, CD274 (PD-L1) and CD40, increased expansion of activated DC populations expressing CD86(hi), CD40(hi), CD83(hi), programmed death ligand 1 (PD-L1)(hi), HLA-DR(hi) or CCR7(hi), as well as elevated secretion of tumour necrosis factor (TNF)-α by DCs. DCs exposed to ATR-107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G-type anti-ATR-107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR-107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules.
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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.