ArticleOncotarget2018
Use of a novel camelid-inspired human antibody demonstrates the importance of MMP-14 to cancer stem cell function in the metastatic process.
Article in Oncotarget, 2018. 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.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.Science translational medicine · 2026Article
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Matrix Metalloproteinase 14 in Corneal Neovascularization.International journal of molecular sciences · 2026Review
- Engineering Single-Chain Antibody Fragment (scFv) Variants Targeting A Disintegrin and Metalloproteinase-17 (ADAM-17).Biomolecules · 2025Article
- Determining key residues of engineered scFv antibody variants with improved MMP-9 binding using deep sequencing and machine learning.Computational and structural biotechnology journal · 2024Article
- Substrate derived sequences act as subsite-blocking motifs in protease inhibitory antibodies.Protein science : a publication of the Protein Society · 2023Article
- Tumor cell-derived asymmetric dimethylarginine regulates macrophage functions and polarization.Cancer cell international · 2022Article
- Matrix metalloproteinases as therapeutic targets in breast cancer.Frontiers in oncology · 2022Review
- Regulation of cancer stem cells in triple negative breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Efficacy of continuous i.v. infusion of recombinant human vascular endothelial growth inhibitor in combination with chemotherapy in patients with advanced lung cancer.American journal of translational research · 2021Article
- Resveratrol inhibits ACHN cells via regulation of histone acetylation.Pharmaceutical biology · 2020Article
- Protease Inhibition Mechanism of Camelid-like Synthetic Human Antibodies.Biochemistry · 2020Article
- Inhibitory Antibodies Designed for Matrix Metalloproteinase Modulation.Molecules (Basel, Switzerland) · 2019Review
- One-step production of fully biotinylated and glycosylated human Fc gamma receptors.Biotechnology progressArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Matrix metalloproteinases (MMPs) are considered excellent targets for cancer therapy because of their important roles in multiple aspects of tumor growth and metastatic spread. However, not all MMPs, or even all activities of specific MMPs, promote cancer. Therefore, there is a need for highly specific inhibitors. Monoclonal antibodies provide the potential for the degree of specificity required, but the isolation of antibodies able to inhibit a specific protease with high selectivity is challenging. Proteolysis specificity lies in recognition of the substrate in or around the active site, which generally forms a concave cleft inaccessible by human IgGs. Inspired by camelid antibodies, which have convex paratopes, we have produced a recombinant human IgG, designated 3A2, which binds in the substrate cleft of MMP-14, inhibiting its activity, but not the activity of highly homologous MMPs. In the 4T1 highly metastatic, syngeneic, orthotopic model of breast cancer, IgG 3A2 markedly inhibited growth of the primary tumor, but more importantly reduced metastatic spread to the lungs and liver by 94%. Stem cells in the tumor population expressed twice as much MMP-14 mRNA as bulk tumor cells. In addition to reducing dissemination of tumor stem cells, as would be expected from inhibition of MMP-14's ability to degrade components of the extracellular matrix, IgG 3A2 also inhibited the ability of individual stem cells to proliferate and produce colonies. We conclude that it is possible to produce antibodies with sufficient specificity for development as therapeutics and that IgG 3A2 has therapeutic potential.
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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.