ArticlemAbs
The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 370 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
370 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Prevalence and clinical relevance of anti-drug antibodies in psoriatic arthritis: a systematic review.RMD open · 2026Pooled it
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Ligelizumab Immunogenicity and Impact on Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety in Patients With Chronic Spontaneous Urticaria.Clinical and translational science · 2026Trial
- Characterization of the VHH-Fc construct rimteravimab in healthy adults and patients hospitalized for mild-to-moderate COVID-19: Two Phase 1 randomized clinical trials.PLoS medicine · 2026Trial
- Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Trial
- Genome-wide pharmacogenetics of anti-drug antibody response to bococizumab highlights key residues in HLA DRB1 and DQB1.Scientific reports · 2022Trial
- Clinical Immunogenicity Evaluation of Eptinezumab, a Therapeutic Humanized Monoclonal Antibody Targeting Calcitonin Gene-Related Peptide (CGRP) for the Preventive Treatment of Migraine.Frontiers in immunology · 2021Trial
- Trial
- Article
- Article
- Computational design and translational development of TCR-mimic scFv antibodies for peptide-HLA neoantigen targeting.npj drug discovery · 2026Review
- Preparation of targeted lipid nanoparticles for precision nucleic acid delivery.Nature protocols · 2026Review
- Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.MedComm · 2026Review
- Developability engineering of scFvs enables robust CAR function under transient mRNA expression.Scientific reports · 2026Article
- A roadmap for systematic humanization of a chimeric antigen receptor: preclinical validation of a humanized CD22 scFv as a model.Experimental hematology · 2026Article
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- Engineering Protease-Resistant Peptides via Non-Canonical Amino Acids: Design Strategies and Biosynthetic Advances.Bioengineering (Basel, Switzerland) · 2026Review
- Liver-Targeted AAV-DJ-hCBS Therapy Achieves Long-Term Correction of Metabolic Imbalance in CBS-Deficient Mice.International journal of molecular sciences · 2026Article
- Rethinking immunogenicity: an integrated approach reveals the PK/PD impact of pre-existing and drug-sustaining ADA.Bioanalysis · 2026Article
- Phage Display Technology: Design, Library Construction, and Panning Strategies for Antibody Development.Biomolecules & therapeutics · 2026Review
310 more citing papers are in PubMed but not listed here.
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monoclonal antibodies represent an attractive therapeutic tool as they are highly specific for their targets, convey effector functions and enjoy robust manufacturing procedures. Humanization of murine monoclonal antibodies has vastly improved their in vivo tolerability. Humanization, the replacement of mouse constant regions and V framework regions for human sequences, results in a significantly less immunogenic product. However, some humanized and even fully human sequence-derived antibody molecules still carry immunological risk. To more fully understand the immunologic potential of humanized and human antibodies, we analyzed CD4(+) helper T cell epitopes in a set of eight humanized antibodies. The antibodies studied represented a number of different VH and VL family members carrying unique CDR regions. In spite of these differences, CD4(+) T cell epitopes were found only in CDR-sequence containing regions. We were able to incorporate up to two amino acid modifications in a single epitope that reduced the immunogenic potential while retaining full biologic function. We propose that immunogenicity will always be present in some antibody molecules due to the nature of the antigen-specific combining sites. A consequence of this result is modifications to reduce immunogenicity will be centered on the affinity-determining regions. Modifications to CDR regions can be designed that reduce the immunogenic potential while maintaining the bioactivity of the antibody molecule.
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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.