ArticleOncotarget2016
Development of a specific affinity-matured exosite inhibitor to MT1-MMP that efficiently inhibits tumor cell invasion in vitro and metastasis in vivo.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 43 citations in OpenAlex.
- Metastasis prevention: targeting causes and roots.Clinical & experimental metastasis · 2022Review
- Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.Frontiers in medicine · 2022Article
- Codon pair optimization (CPO): a software tool for synthetic gene design based on codon pair bias to improve the expression of recombinant proteins in Pichia pastoris.Microbial cell factories · 2021Article
- Membrane-type I matrix metalloproteinase (MT1-MMP), lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2021Review
- Article
- Combined Radiochemotherapy: Metalloproteinases Revisited.Frontiers in oncology · 2021Review
- The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design.Biology · 2020Review
- Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis.Scientific reports · 2020Article
- Identification of specific Tie2 cleavage sites and therapeutic modulation in experimental sepsis.eLife · 2020Article
- Review
- Inhibitory Antibodies Designed for Matrix Metalloproteinase Modulation.Molecules (Basel, Switzerland) · 2019Review
- Reducing proteolytic liability of a MMP-14 inhibitory antibody by site-saturation mutagenesis.Protein science : a publication of the Protein Society · 2019Article
- Mechanisms of Action of Novel Drugs Targeting Angiogenesis-Promoting Matrix Metalloproteinases.Frontiers in immunology · 2019Review
- Monoclonal antibodies against metzincin targets.British journal of pharmacology · 2019Review
- Immunotherapeutic interventions of Triple Negative Breast Cancer.Journal of translational medicine · 2018Review
- A cell surface display fluorescent biosensor for measuring MMP14 activity in real-time.Scientific reports · 2018Article
- MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management.Contrast media & molecular imaging · 2018Article
- Generation of Highly Selective MMP Antibody Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Therapeutic Potential of Matrix Metalloproteinase Inhibition in Breast Cancer.Journal of cellular biochemistry · 2017Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The membrane-associated matrix metalloproteinase-14, MT1-MMP, has been implicated in pericellular proteolysis with an important role in cellular invasion of collagenous tissues. It is substantially upregulated in various cancers and rheumatoid arthritis, and has been considered as a potential therapeutic target. Here, we report the identification of antibody fragments to MT1-MMP that potently and specifically inhibit its cell surface functions. Lead antibody clones displayed inhibitory activity towards pro-MMP-2 activation, collagen-film degradation and gelatin-film degradation, and were shown to bind to the MT1-MMP catalytic domain outside the active site cleft, inhibiting binding to triple helical collagen. Affinity maturation using CDR3 randomization created a second generation of antibody fragments with dissociation constants down to 0.11 nM, corresponding to an improved affinity of 332-fold with the ability to interfere with cell-surface MT1-MMP functions, displaying IC50 values down to 5 nM. Importantly, the new inhibitors were able to inhibit collagen invasion by tumor-cells in vitro and in vivo primary tumor growth and metastasis of MDA-MB-231 cells in a mouse orthotopic xenograft model. Herein is the first demonstration that an inhibitory antibody targeting sites outside the catalytic cleft of MT1-MMP can effectively abrogate its in vivo activity during tumorigenesis and metastasis.
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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.