ArticlePloS one2016
XTEN as Biological Alternative to PEGylation Allows Complete Expression of a Protease-Activatable Killin-Based Cytostatic.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Peptide and Protein Tags for the Half-Life Extension of Therapeutic Agents: A Review Article.The protein journal · 2026Review
- Preclinical Characterization of XB010: A Novel Antibody-Drug Conjugate for the Treatment of Solid Tumors that Targets Tumor-Associated Antigen 5T4.Molecular cancer therapeutics · 2025Article
- Biological Evaluation of Cleavable Linkers in Exatecan-Based Antibody-Drug Conjugates: A Comparative Study of DXd and Exo-Linker Platforms.ACS omega · 2025Article
- Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.Chemical reviews · 2025Review
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- Exo-Cleavable Linkers: Enhanced Stability and Therapeutic Efficacy in Antibody-Drug Conjugates.Journal of medicinal chemistry · 2024Article
- Genetically Encoded XTEN-based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status.Medical oncology (Northwood, London, England) · 2023Review
- Development and characterization of fused human arginase I for cancer therapy.Investigational new drugs · 2023Article
- Human arginase I: a potential broad-spectrum anti-cancer agent.3 Biotech · 2023Review
- From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2023Review
- Human arginase 1, a Jack of all trades?3 Biotech · 2022Review
- The current research status and strategies employed to modify food-derived bioactive peptides.Frontiers in nutrition · 2022Review
- Long-circulating XTEN864-annexin A5 fusion protein for phosphatidylserine-related therapeutic applications.Apoptosis : an international journal on programmed cell death · 2021Article
- Engineering of the Recombinant Expression and PEGylation Efficiency of the Therapeutic Enzyme Human Thymidine Phosphorylase.Frontiers in bioengineering and biotechnology · 2021Article
- Identification of nuclear export signal in KLLN suggests potential role in proteasomal degradation in cancer cells.Oncotarget · 2020Article
- Recent trends in protein and peptide-based biomaterials for advanced drug delivery.Advanced drug delivery reviews · 2020Review
- KLLN-mediated DNA damage-induced apoptosis is associated with regulation of p53 phosphorylation and acetylation in breast cancer cells.Cell death discovery · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased effectiveness and reduced side effects are general goals in drug research, especially important in cancer therapy. The aim of this study was to design a long-circulating, activatable cytostatic drug that is completely producible in E. coli. Crucial for this goal was the novel unstructured polypeptide XTEN, which acts like polyethylene glycol (PEG) but has many important advantages. Most importantly, it can be produced in E. coli, is less immunogenic, and is biodegradable. We tested constructs containing a fragment of Killin as cytostatic/cytotoxic element, a cell-penetrating peptide, an MMP-2 cleavage site for specific activation, and XTEN for long blood circulation and deactivation of Killin. One of three sequence variants was efficiently expressed in E. coli. As typical for XTEN, it allowed efficient purification of the E. coli lysate by a heat step (10 min 75°C) and subsequent anion exchange chromatography using XTEN as purification tag. After 24 h XTEN-Killin reduced the number of viable cells of HT-1080 tumor cell line to 3.8 ±2.0% (p<0.001) compared to untreated controls. In contrast, liver derived non-tumor cells (BRL3A) did not show significant changes in viability. Our results demonstrate the feasibility of completely producing a complex protease-activatable, potentially long-circulating cytostatic/cytotoxic prodrug in E. coli-a concept that could lead to efficient production of highly multifunctional drugs in the future.
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