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Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican

Author(s)
Spreckelsen, Niklas; Fadzen, Colin M.; Hartrampf, Nina; Ghotmi, Yarah; Wolfe, Justin M.; Dubey, Shipra; Yang, Bo Yeun; Kijewski, Marie F.; Wang, Shuyan; Farquhar, Charlotte; Bergmann, Sonja; Zdioruk, Mykola; Wasserburg, J. Roscoe; Scott, Benjamin; Murrell, Emily; Bononi, Fernanda C.; Luyt, Leonard G.; DiCarli, Marcelo; Lamfers, Martine L. M.; Ligon, Keith L.; Chiocca, E. Antonio; Viapiano, Mariano S.; Pentelute, Bradley L.; Lawler, Sean E.; Cho, Choi‐Fong; ... Show more Show less
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Abstract
Glioblastoma multiforme (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg-Bcan, is found only in GBM tissues. Here, dg-Bcan is explored as a molecular target for GBM. In this study, we screened a d-peptide library to identify a small 8-amino acid dg-Bcan-Targeting Peptide (BTP) candidate, called BTP-7 that binds dg-Bcan with high affinity and specificity. BTP-7 is preferentially internalized by dg-Bcan-expressing patient-derived GBM cells. To demonstrate GBM targeting, we radiolabeled BTP-7 with 18F, a radioisotope of fluorine, and found increased radiotracer accumulation in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg-Bcan is an attractive molecular target for GBM, and BTP-7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.
Date issued
2021-01-20
URI
https://hdl.handle.net/1721.1/140314
Department
Massachusetts Institute of Technology. Department of Chemistry
Journal
Advanced Therapeutics
Publisher
Wiley
Citation
Spreckelsen, Niklas, Fadzen, Colin M., Hartrampf, Nina, Ghotmi, Yarah, Wolfe, Justin M. et al. 2021. "Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican." Advanced Therapeutics, 4 (4).
Version: Author's final manuscript
ISSN
2366-3987
2366-3987

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