Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen:
http://dx.doi.org/10.18419/opus-12431
Langanzeige der Metadaten
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Krishna Moorthy, Nivetha | - |
dc.contributor.author | Seifert, Oliver | - |
dc.contributor.author | Eisler, Stephan | - |
dc.contributor.author | Weirich, Sara | - |
dc.contributor.author | Kontermann, Roland E. | - |
dc.contributor.author | Rehm, Markus | - |
dc.contributor.author | Fullstone, Gavin | - |
dc.date.accessioned | 2022-10-07T08:44:43Z | - |
dc.date.available | 2022-10-07T08:44:43Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.other | 1823253245 | - |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-124502 | de |
dc.identifier.uri | http://elib.uni-stuttgart.de/handle/11682/12450 | - |
dc.identifier.uri | http://dx.doi.org/10.18419/opus-12431 | - |
dc.description.abstract | Glioblastoma (GBM) is the most malignant and aggressive form of glioma and is associated with a poor survival rate. Latest generation Tumour Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL)-based therapeutics potently induce apoptosis in cancer cells, including GBM cells, by binding to death receptors. However, the blood–brain barrier (BBB) is a major obstacle for these biologics to enter the central nervous system (CNS). We therefore investigated if antibody-based fusion proteins that combine hexavalent TRAIL and angiopep-2 (ANG2) moieties can be developed, with ANG2 promoting receptor-mediated transcytosis (RMT) across the BBB. We demonstrate that these fusion proteins retain the potent apoptosis induction of hexavalent TRAIL-receptor agonists. Importantly, blood–brain barrier cells instead remained highly resistant to this fusion protein. Binding studies indicated that ANG2 is active in these constructs but that TRAIL-ANG2 fusion proteins bind preferentially to BBB endothelial cells via the TRAIL moiety. Consequently, transport studies indicated that TRAIL-ANG2 fusion proteins can, in principle, be shuttled across BBB endothelial cells, but that low TRAIL receptor expression on BBB endothelial cells interferes with efficient transport. Our work therefore demonstrates that TRAIL-ANG2 fusion proteins remain highly potent in inducing apoptosis, but that therapeutic avenues will require combinatorial strategies, such as TRAIL-R masking, to achieve effective CNS transport. | en |
dc.language.iso | en | de |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/766069 | de |
dc.relation.uri | doi:10.3390/molecules26247582 | de |
dc.rights | info:eu-repo/semantics/openAccess | de |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | de |
dc.subject.ddc | 570 | de |
dc.title | Low-level endothelial TRAIL-receptor expression obstructs the CNS-delivery of angiopep-2 functionalised TRAIL-receptor agonists for the treatment of glioblastoma | en |
dc.type | article | de |
dc.date.updated | 2022-01-03T19:33:34Z | - |
ubs.fakultaet | Chemie | de |
ubs.fakultaet | Energie-, Verfahrens- und Biotechnik | de |
ubs.fakultaet | Fakultäts- und hochschulübergreifende Einrichtungen | de |
ubs.institut | Institut für Biochemie und Technische Biochemie | de |
ubs.institut | Institut für Zellbiologie und Immunologie | de |
ubs.institut | Stuttgart Research Center Systems Biology (SRCSB) | de |
ubs.publikation.seiten | 22 | de |
ubs.publikation.source | Molecules 26 (2021), No. 7582 | de |
ubs.publikation.typ | Zeitschriftenartikel | de |
Enthalten in den Sammlungen: | 04 Fakultät Energie-, Verfahrens- und Biotechnik |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
---|---|---|---|---|
molecules-26-07582-v2.pdf | 4,82 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons