Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican
Name
10.1002-adtp.202000244.pdf
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1.93 MB
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Adobe PDF
Checksum (MD5)
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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
Date Issued
January 20, 2021
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1002/adtp.202000244
