ArticleProtein engineering, design & selection : PEDS2019
Antibody humanization-the Influence of the antibody framework on the CDR-H3 loop ensemble in solution.
Article in Protein engineering, design & selection : PEDS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed.
- Mixture diffusion model for multimodal antibody design.Briefings in bioinformatics · 2026Article
- On the humanization of VHHs: Prospective case studies, experimental and computational characterization of structural determinants for functionality.Protein science : a publication of the Protein Society · 2024Article
- A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy.Antimicrobial agents and chemotherapy · 2024Article
- A universal in silico V(D)J recombination strategy for developing humanized monoclonal antibodies.Journal of nanobiotechnology · 2022Article
- The influence of antibody humanization on shark variable domain (VNAR) binding site ensembles.Frontiers in immunology · 2022Article
- Preparation of a novel EGFR specific immunotoxin and its efficacy of anti-colorectal cancer in vitro and in vivo.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Germline-Dependent Antibody Paratope States and Pairing Specific VFrontiers in immunology · 2021Article
- Mutation of Framework Residue H71 Results in Different Antibody Paratope States in Solution.Frontiers in immunology · 2021Article
- Shark Antibody Variable Domains Rigidify Upon Affinity Maturation-Understanding the Potential of Shark Immunoglobulins as Therapeutics.Frontiers in molecular biosciences · 2021Article
- Antibodies exhibit multiple paratope states influencing VCommunications biology · 2020Article
- Surprisingly Fast Interface and Elbow Angle Dynamics of Antigen-Binding Fragments.Frontiers in molecular biosciences · 2020Article
- Local and Global Rigidification Upon Antibody Affinity Maturation.Frontiers in molecular biosciences · 2020Article
- T-Cell Receptor CDR3 Loop Conformations in Solution Shift the Relative Vα-Vβ Domain Distributions.Frontiers in immunology · 2020Article
- Conformational selection of allergen-antibody complexes-surface plasticity of paratopes and epitopes.Protein engineering, design & selection : PEDS · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Antibody engineering of non-human antibodies has focused on reducing immunogenicity by humanization, being a major limitation in developing monoclonal antibodies. We analyzed four series of antibody binding fragments (Fabs) and a variable fragment (Fv) with structural information in different stages of humanization to investigate the influence of the framework, point mutations and specificity on the complementarity determining region (CDR)-H3 loop dynamics. We also studied a Fv without structural information of the anti-idiotypic antibody Ab2/3H6, because it completely lost its binding affinity upon superhumanization, as an example of a failed humanization. Enhanced sampling techniques in combination with molecular dynamics simulations allow to access micro- to milli-second timescales of the CDR-H3 loop dynamics and reveal kinetic and thermodynamic changes involved in the process of humanization. In most cases, we observe a reduced conformational diversity of the CDR-H3 loop when grafted on a human framework and find a conformational shift of the dominant CDR-H3 loop conformation in solution. A shallow side minimum of the conformational CDR-H3 loop ensemble attached to the murine framework becomes the dominant conformation in solution influenced by the human framework. Additionally, we observe in the case of the failed humanization that the potentially binding competent murine CDR-H3 loop ensemble in solution shows nearly no kinetical or structural overlap with the superhumanized variant, thus explaining the loss of binding.
Indexed as
Identifiers
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.