ArticlemAbs2016
Molecular basis for the antagonistic activity of an anti-CXCR4 antibody.
Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- Antibodies expand the scope of angiotensin receptor pharmacology.Nature chemical biology · 2024Article
- Bone marrow mesenchymal stromal cells support regeneration of intestinal damage in a colitis mouse model, independent of their CXCR4 expression.Clinical and translational science · 2024Article
- Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8.Nature communications · 2023Article
- CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants.GigaScience · 2022Article
- Synthetic nanobodies as angiotensin receptor blockers.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structure-guided discovery of a single-domain antibody agonist against human apelin receptor.Science advances · 2020Article
- Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates.Scientific reports · 2019Article
- Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis.Scientific reports · 2018Article
- A monoclonal antibody raised against a thermo-stabilised βBiochemical pharmacology · 2018Article
- i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor CXCR4.The Journal of biological chemistry · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antagonistic antibodies targeting the G-protein C-X-C chemokine receptor 4 (CXCR4) hold promising therapeutic potential in various diseases. We report for the first time the detailed mechanism of action at a molecular level of a potent anti-CXCR4 antagonistic antibody (MEDI3185). We characterized the MEDI3185 paratope using alanine scanning on all 6 complementary-determining regions (CDRs). We also mapped its epitope using CXCR4 mutagenesis to assess the relative importance of the CXCR4 N-terminal peptide, extracellular loops (ECL) and ligand-binding pocket. We show that the interaction between MEDI3185 and CXCR4 is mediated mostly by CDR3H in MEDI3185 and ECL2 in CXCR4. The MEDI3185 epitope comprises the entire ECL2 sequence, lacks any so-called 'hot-spot' and is remarkably resistant to mutations. The structure of MEDI3185 variable domains was modeled, and suggested a β-strand/β-strand interaction between MEDI3185 CDR3H and CXCR4 ECL2, resulting in direct steric hindrance with CXCR4 ligand SDF-1. These findings may have important implications for designing antibody therapies against CXCR4.
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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.