ArticleMolecular cancer therapeutics2013
Receptor-directed chimeric toxins created by sortase-mediated protein fusion.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Enhanced Vaccine Immunogenicity Enabled by Targeted Cytosolic Delivery of Tumor Antigens into Dendritic Cells.ACS central science · 2023Article
- Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms.Cell reports · 2022Article
- IgG-Engineered Protective Antigen for Cytosolic Delivery of Proteins into Cancer Cells.ACS central science · 2021Article
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- Recent progress in enzymatic protein labelling techniques and their applications.Chemical Society reviews · 2018Review
- Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium.Cell host & microbe · 2018Article
- The activity of myeloid cell-specific VHH immunotoxins is target-, epitope-, subset- and organ dependent.Scientific reports · 2017Article
- Anti-tumor activity of anthrax toxin variants that form a functional translocation pore by intermolecular complementation.Oncotarget · 2017Article
- Identification and characterization of a novel botulinum neurotoxin.Nature communications · 2017Article
- Solid tumor therapy by selectively targeting stromal endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Tumor Targeting and Drug Delivery by Anthrax Toxin.Toxins · 2016Review
- Type VI secretion system sheaths as nanoparticles for antigen display.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- An anthrax toxin variant with an improved activity in tumor targeting.Scientific reports · 2015Article
- Methods for the directed evolution of proteins.Nature reviews. Genetics · 2015Review
- Prodrug applications for targeted cancer therapy.The AAPS journal · 2014Review
- Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric protein toxins that act selectively on cells expressing a designated receptor may serve as investigational probes and/or antitumor agents. Here, we report use of the enzyme sortase A (SrtA) to create four chimeric toxins designed to selectively kill cells bearing the tumor marker HER2. We first expressed and purified: (i) a receptor recognition-deficient form of diphtheria toxin that lacks its receptor-binding domain and (ii) a mutated, receptor-binding-deficient form of anthrax-protective antigen. Both proteins carried at the C terminus the sortase recognition sequence LPETGG and a H₆ affinity tag. Each toxin protein was mixed with SrtA plus either of two HER2-recognition proteins--a single-chain antibody fragment or an Affibody--both carrying an N-terminal G₅ tag. With wild-type SrtA, the fusion reaction between the toxin and receptor-recognition proteins approached completion only after several hours, whereas with an evolved form of the enzyme, SrtA*, the reaction was virtually complete within 5 minutes. The four fusion toxins were purified and shown to kill HER2-positive cells in culture with high specificity. Sortase-mediated ligation of binary combinations of diverse natively folded proteins offers a facile way to produce large sets of chimeric proteins for research and medicine.
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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.