Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies
Abstract Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity‐on‐Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF‐based AcTakine targeted to CD13 enables selective ac...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-01-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201911223 |
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| author | Leander Huyghe Alexander Van Parys Anje Cauwels Sandra Van Lint Stijn De Munter Jennyfer Bultinck Lennart Zabeau Jeroen Hostens An Goethals Nele Vanderroost Annick Verhee Gilles Uzé Niko Kley Frank Peelman Bart Vandekerckhove Peter Brouckaert Jan Tavernier |
| author_facet | Leander Huyghe Alexander Van Parys Anje Cauwels Sandra Van Lint Stijn De Munter Jennyfer Bultinck Lennart Zabeau Jeroen Hostens An Goethals Nele Vanderroost Annick Verhee Gilles Uzé Niko Kley Frank Peelman Bart Vandekerckhove Peter Brouckaert Jan Tavernier |
| author_sort | Leander Huyghe |
| collection | DOAJ |
| description | Abstract Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity‐on‐Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF‐based AcTakine targeted to CD13 enables selective activation of the tumor neovasculature without any detectable toxicity in vivo. Upregulation of adhesion markers supports enhanced T‐cell infiltration leading to control or elimination of solid tumors by, respectively, CAR T cells or a combination therapy with CD8‐targeted type I interferon AcTakine. Co‐treatment with a CD13‐targeted type II interferon AcTakine leads to very rapid destruction of the tumor neovasculature and complete regression of large, established tumors. As no tumor markers are needed, safe and efficacious elimination of a broad range of tumor types becomes feasible. |
| format | Article |
| id | doaj-art-0c182dbd4d474d4e99086c5f110eebd3 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-0c182dbd4d474d4e99086c5f110eebd32025-08-20T03:46:27ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-01-0112211510.15252/emmm.201911223Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapiesLeander Huyghe0Alexander Van Parys1Anje Cauwels2Sandra Van Lint3Stijn De Munter4Jennyfer Bultinck5Lennart Zabeau6Jeroen Hostens7An Goethals8Nele Vanderroost9Annick Verhee10Gilles Uzé11Niko Kley12Frank Peelman13Bart Vandekerckhove14Peter Brouckaert15Jan Tavernier16Cytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityOrionis BiosciencesDepartment of Biomedical Molecular Biology, Ghent UniversityDepartment of Biomedical Molecular Biology, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityCNRS UMR 5235, University of MontpellierOrionis BiosciencesVIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent UniversityDepartment of Biomedical Molecular Biology, Ghent UniversityCytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department of Biomolecular Medicine, Ghent UniversityAbstract Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity‐on‐Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF‐based AcTakine targeted to CD13 enables selective activation of the tumor neovasculature without any detectable toxicity in vivo. Upregulation of adhesion markers supports enhanced T‐cell infiltration leading to control or elimination of solid tumors by, respectively, CAR T cells or a combination therapy with CD8‐targeted type I interferon AcTakine. Co‐treatment with a CD13‐targeted type II interferon AcTakine leads to very rapid destruction of the tumor neovasculature and complete regression of large, established tumors. As no tumor markers are needed, safe and efficacious elimination of a broad range of tumor types becomes feasible.https://doi.org/10.15252/emmm.201911223cancerinterferonsneovasculaturetargeted therapytumor necrosis factor |
| spellingShingle | Leander Huyghe Alexander Van Parys Anje Cauwels Sandra Van Lint Stijn De Munter Jennyfer Bultinck Lennart Zabeau Jeroen Hostens An Goethals Nele Vanderroost Annick Verhee Gilles Uzé Niko Kley Frank Peelman Bart Vandekerckhove Peter Brouckaert Jan Tavernier Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies EMBO Molecular Medicine cancer interferons neovasculature targeted therapy tumor necrosis factor |
| title | Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies |
| title_full | Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies |
| title_fullStr | Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies |
| title_full_unstemmed | Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies |
| title_short | Safe eradication of large established tumors using neovasculature‐targeted tumor necrosis factor‐based therapies |
| title_sort | safe eradication of large established tumors using neovasculature targeted tumor necrosis factor based therapies |
| topic | cancer interferons neovasculature targeted therapy tumor necrosis factor |
| url | https://doi.org/10.15252/emmm.201911223 |
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