ArticlemAbs2014
Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge.
Article in mAbs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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
80 citing papers in PubMed, 120 citations in OpenAlex.
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- Letter to the editor regarding "Improvement of tumor-to-blood ratio of radioimmunoconjugates by poly(ethyleneimine)-containing chelating agent".Annals of nuclear medicine · 2026Article
- Antibody Humanization.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Probing the extent of importin-α targeting of the TAF8 NLS by eliminating its cationic net-charge.Protein science : a publication of the Protein Society · 2025Article
- The characterization of variable new antigen receptors targeting FAP isolated from a novel immunized library.Communications biology · 2025Article
- Investigating the impact of synonymous gene recoding on a recombinantly expressed monoclonal antibody under different process parameters.Bioengineering & translational medicine · 2025Article
- Improvement of tumor-to-blood ratio of radioimmunoconjugates by poly(ethyleneimine)-containing chelating agent.Annals of nuclear medicine · 2025Article
- Development of FAP-targeted theranostics discovered by next-generation sequencing-augmented mining of a novel immunized VNAR library.bioRxiv : the preprint server for biology · 2025Article
- Single-Domain Antibodies-Novel Tools to Study and Treat Allergies.International journal of molecular sciences · 2024Review
- Long-Acting Strategies for Antibody Drugs: Structural Modification, Controlling Release, and Changing the Administration Route.European journal of drug metabolism and pharmacokinetics · 2024Review
- Article
- Nonspecificity fingerprints for clinical-stage antibodies in solution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tau-targeting therapies for Alzheimer disease: current status and future directions.Nature reviews. Neurology · 2023Review
- Nanobody-peptide-conjugate (NPC) for passive immunotherapy against SARS-CoV-2 variants of concern (VoC): a prospective pan-coronavirus therapeutics.Molecular diversity · 2023Article
- Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01.Nature communications · 2023Article
- A biomimetic chip to assess subcutaneous bioavailability of monoclonal antibodies in humans.PNAS nexus · 2023Article
- Physiologically Based Pharmacokinetic Modeling to Characterize the Effect of Molecular Charge on Whole-Body Disposition of Monoclonal Antibodies.The AAPS journal · 2023Article
- SUMO: In Silico Sequence Assessment Using Multiple Optimization Parameters.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Radiolabelling small and biomolecules for tracking and monitoring.RSC advances · 2022Review
- Monoclonal Antibody Engineering and Design to Modulate FcRn Activities: A Comprehensive Review.International journal of molecular sciences · 2022Review
20 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
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This antibody binds to the rat recycling receptor FcRn as expected for a human IgG1 antibody and does not display non-specific binding to baculovirus particles in an assay that is correlated with fast clearance in cynomolgus monkey. The antigen is not expressed in rat so target-dependent clearance does not contribute to PK. Removal of the affinity maturation changes (hu5B3.κ1VH3.v1) did not restore normal clearance. The antibody was re-humanized on a κ4, VH1 framework and the non-affinity matured version (hu5B3.κ4VH1.v1) was shown to have normal clearance (8.5 mL/day/kg). Since the change in framework results in a lower pI, primarily due to more negative charge on the κ4 template, the effect of additional charge variation on antibody PK was tested by incorporating substitutions obtained through phage display affinity maturation of hu5B3.κ1VH3.v1. A variant having a pI of 8.61 gave very fast clearance (140 mL/day/kg) whereas a molecule with pI of 6.10 gave slow clearance (5.8 mL/kg/day). Both antibodies exhibited comparable binding to rat FcRn, but biodistribution experiments showed that the high pI variant was catabolized in liver and spleen. These results suggest antibody charge can have an effect on PK through alterations in antibody catabolism independent of FcRn-mediated recycling. Furthermore, introduction of affinity maturation changes into the lower pI framework yielded a candidate with PK and virus neutralization properties suitable for clinical development.
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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.