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Identification and Tumour-Binding Properties of a Peptide with High Affinity to the Disialoganglioside GD2
Mueller, Jan ;  Reichel, Robin ;  Vogt, Sebastian ;  Mueller, Stefan P. ;  Sauerwein, Wolfgang ;  Brandau, Wolfgang ;  Eggert, Angelika ;  Schramm, Alexander

HaupttitelIdentification and Tumour-Binding Properties of a Peptide with High Affinity to the Disialoganglioside GD2
AutorMueller, Jan
AutorReichel, Robin
AutorVogt, Sebastian
AutorMueller, Stefan P.
AutorSauerwein, Wolfgang
AutorBrandau, Wolfgang
AutorEggert, Angelika
AutorSchramm, Alexander
Seitenzahl16 S.
DDC610 Medizin und Gesundheit
Auch erschienen inPLoS ONE. - 11 (2016), 10, Artikel Nr. e0163648
ZusammenfassungNeuroectodermal tumours are characterized by aberrant processing of disialogangliosides concomitant with high expression of GD2 or GD3 on cell surfaces. Antibodies targeting GD2 are already in clinical use for therapy of neuroblastoma, a solid tumour of early childhood. Here, we set out to identify peptides with high affinity to human disialoganglioside GD2. To this end, we performed a combined in vivo and in vitro screen using a recombinant phage displayed peptide library. We isolated a phage displaying the peptide sequence WHWRLPS that specifically binds to the human disialoganglioside GD2. Binding specificity was confirmed by mutational scanning and by comparative analyses using structurally related disialogangliosides. In vivo, significant enrichment of phage binding to xenografts of human neuroblastoma cells in mice was observed. Tumour-specific phage accumulation could be blocked by intravenous coinjection of the corresponding peptide. Comparative pharmacokinetic analyses revealed higher specific accumulation of 68Ga-labelled GD2-binding peptide compared to 111In-labelled peptide in xenografts of human neuroblastoma. In contrast to 124I-MIBG, which is currently evaluated as a neuroblastoma marker in PET/CT, 68Ga-labelled GD2-specific peptide spared the thyroid but was enriched in the kidneys, which could be partially blocked by infusion of amino acids.In summary, we here report on a novel tumour-homing peptide that specifically binds to the disialoganglioside GD2, accumulates in xenografts of neuroblastoma cells in mice and bears the potential for tumour detection using PET/CT. Thus, this peptide may serve as a new scaffold for diagnosing GD2-positive tumours of neuroectodermal origin.
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Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Erscheinungsjahr2016
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am17.11.2016 - 08:25:12
Letzte Änderung17.11.2016 - 08:31:08
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000025714
DOI10.1371/journal.pone.0163648
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