ReviewExpert review of clinical pharmacology2013
Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics.
Review in Expert review of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 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
- The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review.International journal of molecular sciences · 2026Review
- Incidence and implications of anti-rituximab antibodies in nephropathies and other immune-mediated diseases: a narrative review.Frontiers in immunology · 2026Review
- Anti-Drug Antibody Response to Therapeutic Antibodies and Potential Mitigation Strategies.Biomedicines · 2025Review
- Individual and population-level variability in HLA-DR associated immunogenicity risk of biologics used for the treatment of rheumatoid arthritis.Frontiers in immunology · 2024Article
- Development of CAR T Cell Therapy in Children-A Comprehensive Overview.Journal of clinical medicine · 2022Review
- Potent germline-like monoclonal antibodies: rapid identification of promising candidates for antibody-based antiviral therapy.Antibody therapeutics · 2021Article
- Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Optimization of therapeutic antibodies.Antibody therapeutics · 2021Review
- Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity.Immunology · 2018Article
- Identifying the Epitope Regions of Therapeutic Antibodies Based on Structure Descriptors.International journal of molecular sciences · 2017Article
- Development of unique cytotoxic chimeric antigen receptors based on human scFv targeting B7H6.Protein engineering, design & selection : PEDS · 2017Article
- Lysibodies are IgG Fc fusions with lysin binding domains targetingProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence.BMJ open · 2016Article
- Biosimilars in rheumatic diseases: structural and functional variability that may impact clinical and regulatory decisions.Clinical rheumatology · 2016Review
- Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins.Journal of immunology research · 2016Review
- In Vivo Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model.PloS one · 2016Article
- Sialic acid-binding protein Sp2CBMTD protects mice against lethal challenge with emerging influenza A (H7N9) virus.Antimicrobial agents and chemotherapy · 2015Article
- H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance.Human vaccines & immunotherapeutics · 2015Article
- Removing T-cell epitopes with computational protein design.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target 'foreign' sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xeno-sequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics 'quality by design', may lead to the development of ever more clinically effective, but less immunogenic, biologics.
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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.