ArticleScientific reports2017
Selective antibody activation through protease-activated pro-antibodies that mask binding sites with inhibitory domains.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Article
- Engineering a Glucose-Responsive Glucagon Prodrug Through Arginine-Phenylboronic Acid Pendant Modification.Small science · 2026Article
- Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- Past, present and future of drug conjugates for cancer therapy.Nature cancer · 2025Review
- A facile yeast-display approach for antibody mask discovery.Protein engineering, design & selection : PEDS · 2025Article
- A masking clamp for conditional activation of therapeutic antibodies.Frontiers in immunology · 2025Article
- A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.Inflammation and regeneration · 2023Article
- Therapeutic antibodies for precise cancer immunotherapy: current and future perspectives.Medical review (2021) · 2022Review
- The present and future of immunocytokines for cancer treatment.Cellular and molecular life sciences : CMLS · 2022Review
- Antibody variable region engineering for improving cancer immunotherapy.Cancer communications (London, England) · 2022Review
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
- Switchable immune modulator for tumor-specific activation of anticancer immunity.Science advances · 2021Article
- The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control.ACS central science · 2021Review
- Enhancement of tumor tropism of mPEGylated nanoparticles by anti-mPEG bispecific antibody for ovarian cancer therapy.Scientific reports · 2021Article
- Activatable Zymography Probes EnableCancer research · 2021Article
- Ab locks for improving the selectivity and safety of antibody drugs.Journal of biomedical science · 2020Review
- Computational Design of an Allosteric Antibody Switch by Deletion and Rescue of a Complex Structural Constellation.ACS central science · 2020Article
- ISOPTJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2019Article
- Optical Control of Antibody Activity by Using Photocleavable Bivalent Peptide-DNA Locks.Chembiochem : a European journal of chemical biology · 2019Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic injection of therapeutic antibodies may cause serious adverse effects due to on-target toxicity to the antigens expressed in normal tissues. To improve the targeting selectivity to the region of disease sites, we developed protease-activated pro-antibodies by masking the binding sites of antibodies with inhibitory domains that can be removed by proteases that are highly expressed at the disease sites. The latency-associated peptide (LAP), C2b or CBa of complement factor 2/B were linked, through a substrate peptide of matrix metalloproteinase-2 (MMP-2), to an anti-epidermal growth factor receptor (EGFR) antibody and an anti-tumor necrosis factor-α (TNF-α) antibody. Results showed that all the inhibitory domains could be removed by MMP-2 to restore the binding activities of the antibodies. LAP substantially reduced (53.8%) the binding activity of the anti-EGFR antibody on EGFR-expressing cells, whereas C2b and CBa were ineffective (21% and 9.3% reduction, respectively). Similarly, LAP also blocked 53.9% of the binding activity of the anti-TNF-α antibody. Finally, molecular dynamic simulation showed that the masking efficiency of LAP, C2b and CBa was 33.7%, 10.3% and -5.4%, respectively, over the binding sites of the antibodies. This strategy may aid in designing new protease-activated pro-antibodies that attain high therapeutic potency yet reduced systemic on-target toxicity.
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